Lung cancer
Overview
 
Lung cancer is a disease characterized by uncontrolled cell growth
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...

 in tissues
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...

 of the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

. If left untreated, this growth can spread beyond the lung in a process called metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary lung cancers, are carcinomas that derive from epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

 cells. Worldwide, lung cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 is the most common cause of cancer-related death in men and women, and is responsible for 1.3 million deaths
annually, as of 2004.
Encyclopedia
Lung cancer is a disease characterized by uncontrolled cell growth
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...

 in tissues
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...

 of the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

. If left untreated, this growth can spread beyond the lung in a process called metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary lung cancers, are carcinomas that derive from epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

 cells. Worldwide, lung cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 is the most common cause of cancer-related death in men and women, and is responsible for 1.3 million deaths
annually, as of 2004. The most common symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...

s are shortness of breath, coughing (including coughing up blood
Hemoptysis
Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...

), and weight loss.

The main types of lung cancer are small-cell lung cancer (SCLC), also called oat cell cancer, and non-small-cell lung cancer (NSCLC). The most common cause of lung cancer is long-term exposure to tobacco smoke
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...

. Nonsmokers account for 15% of lung cancer cases, and these cases are often attributed to a combination of genetic factors
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

, radon
Radon
Radon is a chemical element with symbol Rn and atomic number 86. It is a radioactive, colorless, odorless, tasteless noble gas, occurring naturally as the decay product of uranium or thorium. Its most stable isotope, 222Rn, has a half-life of 3.8 days...

 gas, asbestos
Asbestos
Asbestos is a set of six naturally occurring silicate minerals used commercially for their desirable physical properties. They all have in common their eponymous, asbestiform habit: long, thin fibrous crystals...

, and air pollution
Air pollution
Air pollution is the introduction of chemicals, particulate matter, or biological materials that cause harm or discomfort to humans or other living organisms, or cause damage to the natural environment or built environment, into the atmosphere....

 including secondhand smoke
Passive smoking
Passive smoking is the inhalation of smoke, called secondhand smoke or environmental tobacco smoke , from tobacco products used by others. It occurs when tobacco smoke permeates any environment, causing its inhalation by people within that environment. Exposure to secondhand tobacco smoke causes...

.

Lung cancer may be seen on chest radiograph and computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

 (CT scan). The diagnosis
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...

 is confirmed with a biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

. This is usually performed by bronchoscopy
Bronchoscopy
Bronchoscopy is a technique of visualizing the inside of the airways for diagnostic and therapeutic purposes. An instrument is inserted into the airways, usually through the nose or mouth, or occasionally through a tracheostomy. This allows the practitioner to examine the patient's airways for...

 or CT-guided biopsy. Treatment and prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...

 depend on the histological
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...

 type of cancer, the stage (degree of spread), and the patient's general wellbeing, measured by performance status
Performance status
In medicine , performance status is an attempt to quantify cancer patients' general well-being and activities of daily life. This measure is used to determine whether they can receive chemotherapy, whether dose adjustment is necessary, and as a measure for the required intensity of palliative care...

. Common treatments include surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

, chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

, and radiotherapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...

. NSCLC is sometimes treated with surgery, whereas SCLC usually responds better to chemotherapy and radiation therapy. This is partly because SCLC often spreads quite early, and these treatments are generally better at getting to cancer cells that have spread to other parts of the body.

Survival depends on stage, overall health, and other factors, but overall 14% of people diagnosed with lung cancer survive
Survival rate
In biostatistics, survival rate is a part of survival analysis, indicating the percentage of people in a study or treatment group who are alive for a given period of time after diagnosis...

 five years after the diagnosis.

Signs and symptoms

Symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...

s that may suggest lung cancer include:

If the cancer grows in the airway
Airway
The pulmonary airway comprises those parts of the respiratory system through which air flows, conceptually beginning at the nose and mouth, and terminating in the alveoli...

, it may obstruct airflow, causing breathing difficulties
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...

. The obstruction can lead to accumulation of secretions behind the blockage, and predispose to pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

. Many lung cancers have a rich blood supply. The surface of the cancer may be fragile, leading to bleeding from the cancer into the airway. This blood may subsequently be coughed up.

Depending on the type of tumor, so-called paraneoplastic phenomena
Paraneoplastic syndrome
A paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors excreted by tumor cells or by an immune response against the tumor...

 may initially attract attention to the disease. In lung cancer, these phenomena may include Lambert-Eaton myasthenic syndrome
Lambert-Eaton myasthenic syndrome
Lambert–Eaton myasthenic syndrome is a rare autoimmune disorder that is characterised by muscle weakness of the limbs...

 (muscle weakness due to auto-antibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone
Syndrome of inappropriate antidiuretic hormone
The syndrome of inappropriate antidiuretic hormone hypersecretion is characterized by excessive release of antidiuretic hormone from the posterior pituitary gland or another source. The result is hyponatremia and sometimes fluid overload...

 (SIADH). Tumors in the top (apex) of the lung, known as Pancoast tumor
Pancoast tumor
A Pancoast tumor, also called a pulmonary sulcus tumor or superior sulcus tumor, is a tumor of the pulmonary apex. It is a type of lung cancer defined primarily by its location situated at the top end of either the right or left lung. It typically spreads to nearby tissues such as the ribs and...

s, may invade the local part of the sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...

, leading to changed sweating patterns and eye muscle problems (a combination known as Horner's syndrome
Horner's syndrome
Horner's syndrome is the combination of drooping of the eyelid and constriction of the pupil , sometimes accompanied by decreased sweating of the face on the same side; redness of the conjunctiva of the eye is often also present...

) as well as muscle weakness in the hands due to invasion of the brachial plexus
Brachial plexus
The brachial plexus is a network of nerve fibers, running from the spine, formed by the ventral rami of the lower four cervical and first thoracic nerve roots...

.

Many of the symptoms of lung cancer (bone pain
Bone pain
Bone pain is a debilitating form of pain emanating from the bone tissue. It occurs as a result of a wide range of diseases and/or physical conditions and may severely impair the quality of life for patients who suffer from it...

, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, and weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

) are nonspecific; in the elderly, these may be attributed to comorbid illness
Comorbidity
In medicine, comorbidity is either the presence of one or more disorders in addition to a primary disease or disorder, or the effect of such additional disorders or diseases.- In medicine :...

. In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 include the brain, bone, adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

s, contralateral (opposite) lung, liver, pericardium
Pericardium
The pericardium is a double-walled sac that contains the heart and the roots of the great vessels.-Layers:...

, and kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

s. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph.

Causes

The main causes of any cancer include carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...

s (such as those in tobacco smoke), ionizing radiation
Ionizing radiation
Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...

, and viral infection. This exposure causes cumulative changes to the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 in the tissue lining the bronchi of the lungs (the bronchial epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

). As more tissue becomes damaged, eventually a cancer develops.

Smoking

Smoking
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...

, particularly of cigarette
Cigarette
A cigarette is a small roll of finely cut tobacco leaves wrapped in a cylinder of thin paper for smoking. The cigarette is ignited at one end and allowed to smoulder; its smoke is inhaled from the other end, which is held in or to the mouth and in some cases a cigarette holder may be used as well...

s, is by far the main contributor to lung cancer. Cigarette smoke contains over 60 known carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...

s, including radioisotopes from the radon
Radon
Radon is a chemical element with symbol Rn and atomic number 86. It is a radioactive, colorless, odorless, tasteless noble gas, occurring naturally as the decay product of uranium or thorium. Its most stable isotope, 222Rn, has a half-life of 3.8 days...

 decay sequence, nitrosamine
Nitrosamine
Nitrosamines are chemical compounds of the chemical structure R1N-N=O, some of which are carcinogenic.-Usages:Nitrosamines are used in manufacture of some cosmetics, pesticides, and in most rubber products. -Occurrences:...

, and benzopyrene
Benzopyrene
Benzo[a]pyrene, C20H12, is a five-ring polycyclic aromatic hydrocarbon whose metabolites are mutagenic and highly carcinogenic. Benzo[a]pyrene is listed as a Group 1 carcinogen by the IARC. It belongs to a class of polycyclic aromatic compounds known as benzopyrenes, which consist of a benzene...

. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue. Across the developed world, 91% of lung cancer deaths in men during the year 2000 were attributed to smoking (71% for women). In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women). Among male smokers, the lifetime risk of developing lung cancer is 17.2%; among female smokers, the risk is 11.6%. This risk is significantly lower in nonsmokers: 1.3% in men and 1.4% in women.

Women who smoke (former smokers and current smokers) and take hormone therapy are at a much higher risk of dying of lung cancer. In a study by Chlebowski et al. published in 2009, the women taking hormones were about 60% more likely to die of lung cancer than the women taking a placebo. Not surprisingly, the risk was highest for current smokers, followed by past smokers, and lowest for those who have never smoked. Among the women who smoked (former or current smokers), 3.4% of those taking hormone therapy died of lung cancer compared to 2.3% for women taking the placebo.

The time a person smokes (as well as rate of smoking) increases the person's chance of developing lung cancer. If a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually removed. In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers, and that patients who smoke at the time of diagnosis have shorter survival times than those who have quit.

Passive smoking
Passive smoking
Passive smoking is the inhalation of smoke, called secondhand smoke or environmental tobacco smoke , from tobacco products used by others. It occurs when tobacco smoke permeates any environment, causing its inhalation by people within that environment. Exposure to secondhand tobacco smoke causes...

—the inhalation of smoke from another's smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be classified as someone living or working with a smoker. Studies from the U.S.,*
*
*
*
* Europe, the UK,* and Australia have consistently shown a significant increase in relative risk
Relative risk
In statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....

 among those exposed to passive smoke. Recent investigation of sidestream smoke
Sidestream smoke
Sidestream smoke is smoke which goes into the air directly from a burning cigarette, cigar or smoking pipe. Sidestream smoke is the main component of Environmental Tobacco Smoke , also known as passive smoking The chemical constituents of sidestream smoke are different from those of directly...

 suggests that it is more dangerous than direct smoke inhalation.

10–15% of lung cancer patients have never smoked. That means between 20,000 to 30,000 never-smokers are diagnosed with lung cancer in the United States each year. Because of the five-year survival rate, each year in the U.S. more never-smokers die of lung cancer than do patients of leukemia, ovarian cancer, or AIDS.

Radon gas

Radon
Radon
Radon is a chemical element with symbol Rn and atomic number 86. It is a radioactive, colorless, odorless, tasteless noble gas, occurring naturally as the decay product of uranium or thorium. Its most stable isotope, 222Rn, has a half-life of 3.8 days...

 is a colorless and odorless gas
Gas
Gas is one of the three classical states of matter . Near absolute zero, a substance exists as a solid. As heat is added to this substance it melts into a liquid at its melting point , boils into a gas at its boiling point, and if heated high enough would enter a plasma state in which the electrons...

 generated by the breakdown of radioactive radium
Radium
Radium is a chemical element with atomic number 88, represented by the symbol Ra. Radium is an almost pure-white alkaline earth metal, but it readily oxidizes on exposure to air, becoming black in color. All isotopes of radium are highly radioactive, with the most stable isotope being radium-226,...

, which in turn is the decay product of uranium
Uranium
Uranium is a silvery-white metallic chemical element in the actinide series of the periodic table, with atomic number 92. It is assigned the chemical symbol U. A uranium atom has 92 protons and 92 electrons, of which 6 are valence electrons...

, found in the Earth's crust
Crust (geology)
In geology, the crust is the outermost solid shell of a rocky planet or natural satellite, which is chemically distinct from the underlying mantle...

. The radiation decay products ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...

ize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer in the general population, after smoking with the risk increasing 8–16% for every 100 Bq
Becquerel
The becquerel is the SI-derived unit of radioactivity. One Bq is defined as the activity of a quantity of radioactive material in which one nucleus decays per second. The Bq unit is therefore equivalent to an inverse second, s−1...

/
Cubic metre
The cubic metre is the SI derived unit of volume. It is the volume of a cube with edges one metre in length. An alternative name, which allowed a different usage with metric prefixes, was the stère...

 increase in the radon concentration. Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall
Cornwall
Cornwall is a unitary authority and ceremonial county of England, within the United Kingdom. It is bordered to the north and west by the Celtic Sea, to the south by the English Channel, and to the east by the county of Devon, over the River Tamar. Cornwall has a population of , and covers an area of...

 in the UK (which has granite
Granite
Granite is a common and widely occurring type of intrusive, felsic, igneous rock. Granite usually has a medium- to coarse-grained texture. Occasionally some individual crystals are larger than the groundmass, in which case the texture is known as porphyritic. A granitic rock with a porphyritic...

 as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency
United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...

 (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 picocuries per liter (pCi/L) (148 Bq/m³). Iowa
Iowa
Iowa is a state located in the Midwestern United States, an area often referred to as the "American Heartland". It derives its name from the Ioway people, one of the many American Indian tribes that occupied the state at the time of European exploration. Iowa was a part of the French colony of New...

 has the highest average radon concentration in the United States; studies performed there have demonstrated a 50% increased lung cancer risk, with prolonged radon exposure above the EPA's action level of 4 pCi/L.

Asbestos

Asbestos
Asbestos
Asbestos is a set of six naturally occurring silicate minerals used commercially for their desirable physical properties. They all have in common their eponymous, asbestiform habit: long, thin fibrous crystals...

 can cause a variety of lung diseases, including lung cancer. There is a synergistic
Synergy
Synergy may be defined as two or more things functioning together to produce a result not independently obtainable.The term synergy comes from the Greek word from , , meaning "working together".-Definitions and usages:...

 effect between tobacco smoking and asbestos in the formation of lung cancer. In the UK, asbestos accounts for 2–3% of male lung cancer deaths. Asbestos can also cause cancer of the pleura, called mesothelioma
Mesothelioma
Mesothelioma, more precisely malignant mesothelioma, is a rare form of cancer that develops from the protective lining that covers many of the body's internal organs, the mesothelium...

 (which is different from lung cancer).

Viruses

Virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

es are known to cause lung cancer in animals, and recent evidence suggests similar potential in humans. Implicated viruses include human papillomavirus
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...

, JC virus
JC virus
The JC virus or John Cunningham virus is a type of human polyomavirus and is genetically similar to BK virus and SV40. It was discovered in 1971 and named using the two initials of a patient with progressive multifocal leukoencephalopathy...

, simian virus 40
SV40
SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a polyomavirus that is found in both monkeys and humans...

 (SV40), BK virus
BK virus
The BK virus is a member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon, with the exception of the immunocompromised and the immunosuppressed.-History:...

, and cytomegalovirus
Cytomegalovirus
Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...

. These viruses may affect the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...

 and inhibit apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

, allowing uncontrolled cell division.

Particulate matter

Studies of the American Cancer Society cohort directly link the exposure to particulate matter with lung cancer. For example, if the concentration of particles in the air increases by only 1%, the risk of developing a lung cancer increases by 14%. Further, it has been established that particle size matters, as ultrafine particles penetrate further into the lungs.

Pathogenesis

Similar to many other cancers, lung cancer is initiated by activation of oncogene
Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...

s or inactivation of tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...

s. Oncogenes are gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s that are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens. Mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

s in the K-ras proto-oncogene are responsible for 10–30% of lung adenocarcinomas. The epidermal growth factor receptor
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...

 (EGFR) regulates cell proliferation, apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

, angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...

, and tumor invasion. Mutations and amplification of EGFR are common in non-small-cell lung cancer and provide the basis for treatment with EGFR-inhibitors. Her2/neu
HER2/neu
HER-2 also known as proto-oncogene Neu, receptor tyrosine-protein kinase erbB-2, CD340 or p185 is an enzyme that in humans is encoded by the ERBB2 gene. Over expression of this gene is correlated with higher aggressiveness in breast cancers...

 is affected less frequently. Chromosomal
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

 damage can lead to loss of heterozygosity
Loss of heterozygosity
Loss of heterozygosity in a cell is the loss of normal function of one allele of a gene in which the other allele was already inactivated. This term is mostly used in the context of oncogenesis; after an inactivating mutation in one allele of a tumor suppressor gene occurs in the parent's germline...

. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q, and 17p are particularly common in small-cell lung carcinoma. The p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

tumor suppressor gene, located on chromosome 17p, is affected in 60-75% of cases. Other genes that are often mutated or amplified are c-MET
C-MET
c-Met is a proto-oncogene that encodes a protein known as hepatocyte growth factor receptor . The hepatocyte growth factor receptor protein possesses tyrosine-kinase activity...

, NKX2-1, LKB1, PIK3CA, and BRAF
BRAF (gene)
Serine/threonine-protein kinase B-Raf or simply B-Raf, also known as proto-oncogene B-Raf or v-Raf murine sarcoma viral oncogene homolog B1, is a protein that in humans is encoded by the BRAF gene...

.

Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s coding for interleukin
Interleukin
Interleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...

-1, cytochrome P450, apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 promoters such as caspase
Caspase
Caspases, or cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases are a family of cysteine proteases that play essential roles in apoptosis , necrosis, and inflammation....

-8, and DNA repair molecules such as XRCC1
XRCC1
XRCC1 is a DNA repair protein.It complexes with DNA ligase III.-Interactions:XRCC1 has been shown to interact with PARP2, DNA polymerase beta, Aprataxin, Oxoguanine glycosylase, PCNA, APEX1, PNKP and PARP1.-Further reading:-External links:...

. People with these polymorphisms are more likely to develop lung cancer after exposure to carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...

s.

A recent study suggested that the MDM2
Mdm2
Mdm2 is an important negative regulator of the p53 tumor suppressor. It is the name of a gene as well as the protein encoded by that gene. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain of the p53 tumor suppressor and an inhibitor of...

 309G allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

 is a low-penetrant risk factor for developing lung cancer in Asians.

Diagnosis

Performing a chest radiograph is the first step if a patient reports symptoms that may suggest lung cancer. This may reveal an obvious mass, widening of the mediastinum
Mediastinum
The mediastinum is a non-delineated group of structures in the thorax, surrounded by loose connective tissue. It is the central compartment of the thoracic cavity...

 (suggestive of spread to lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

s there), atelectasis
Atelectasis
Atelectasis is defined as the collapse or closure of alveoli resulting in reduced or absent gas exchange. It may affect part or all of one lung. It is a condition where the alveoli are deflated, as distinct from pulmonary consolidation.It is a very common finding in chest x-rays and other...

 (collapse), consolidation (pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

), or pleural effusion
Pleural effusion
Pleural effusion is excess fluid that accumulates between the two pleural layers, the fluid-filled space that surrounds the lungs. Excessive amounts of such fluid can impair breathing by limiting the expansion of the lungs during ventilation.-Pathophysiology:...

. If there are no radiographic findings but the suspicion is high (such as a heavy smoker with blood-stained sputum), bronchoscopy
Bronchoscopy
Bronchoscopy is a technique of visualizing the inside of the airways for diagnostic and therapeutic purposes. An instrument is inserted into the airways, usually through the nose or mouth, or occasionally through a tracheostomy. This allows the practitioner to examine the patient's airways for...

 and/or a CT scan may provide the necessary information. Bronchoscopy or CT-guided biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

 is often used to identify the tumor type.

Abnormal findings in cells ("atypia
Atypia
Atypia is a clinical term for abnormality in a cell. The term is medical jargon for an atypical cell. Atypia: Etymology: Gk, a + typos, without type; a condition of being irregular or nonstandard....

") in sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....

 are associated with an increased risk of lung cancer. Sputum cytologic
Cytopathology
Cytopathology is a branch of pathology that studies and diagnoses diseases on the cellular level. The discipline was founded by Rudolf Virchow in 1858. A common application of cytopathology is the Pap smear, used as a screening tool, to detect precancerous cervical lesions and prevent cervical...

 examination combined with other screening examinations may have a role in the early detection of lung cancer.

The differential diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

 for patients who present with abnormalities on chest radiograph includes lung cancer as well as nonmalignant diseases. These include infectious causes such as tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

 or pneumonia, or inflammatory conditions such as sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...

. These diseases can result in mediastinal
Mediastinum
The mediastinum is a non-delineated group of structures in the thorax, surrounded by loose connective tissue. It is the central compartment of the thoracic cavity...

 lymphadenopathy
Lymphadenopathy
Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....

 or lung nodules
Nodule (medicine)
For use of the term nodule in dermatology, see Nodule In medicine, a nodule refers to a relatively hard, roughly spherical abnormal structure....

, and sometimes mimic lung cancers. Lung cancer can also be an incidental finding
Incidentaloma
In medicine, an incidentaloma is a tumor found by coincidence without clinical symptoms or suspicion. It is a common problem: up to 7% of all patients over 60 may harbor a benign growth, often of the adrenal gland, which is detected when diagnostic imaging is used for the analysis of unrelated...

: a solitary pulmonary nodule
Solitary pulmonary nodule
In radiology, a solitary pulmonary nodule or coin lesion is a mass in the lung smaller than 3 centimeters in diameter. It can be an incidental finding found in up to 0.2% of chest X-rays and around 1% of CT scans....

 (also called a coin lesion) on a chest radiograph or CT scan taken for an unrelated reason. The definitive diagnosis of lung cancer and its classification (described above) is based on examination of the suspicious tissue under the microscope
Microscope
A microscope is an instrument used to see objects that are too small for the naked eye. The science of investigating small objects using such an instrument is called microscopy...

 by a pathologist.

Classification

Lung cancers are classified according to histological type
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...

. This classification has important implications for clinical management and prognosis of the disease. The vast majority of lung cancers are carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...

s—malignancies that arise from epithelial cells. The two most prevalent histological types of lung carcinoma, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope
Microscope
A microscope is an instrument used to see objects that are too small for the naked eye. The science of investigating small objects using such an instrument is called microscopy...

, are non-small-cell and small-cell lung carcinoma. The non-small-cell type is the most prevalent by far (see accompanying table).
style="background:#E5AFAA;"|Frequency of histological types of lung cancer
Histological type Frequency (%)
Non-small-cell lung carcinoma 80.4
Small-cell lung carcinoma 16.8
Carcinoid
Carcinoid
Carcinoid is a slow-growing type of neuroendocrine tumor, originating in the cells of the neuroendocrine system.In 2000, the World Health Organization redefined "carcinoid", but this new definition has not been accepted by all practitioners. This has led to some complexity in distinguishing...

0.8
Sarcoma
Sarcoma
A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...

0.1
Unspecified lung cancer 1.9


Cancer found outside of the lung may be determined to have arisen within the lung, as lung cancers that metastasize, i.e. spread, often retain a cell marker profile that allow a pathologist to say, with a good deal of certainty, that the tumor arose from the lung, i.e. is a primary lung cancer. Primary lung cancers of adenocarcinoma histology typically have nuclear
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

 immunostaining with TTF-1.

Non-small-cell lung carcinoma

The non-small-cell lung carcinomas (NSCLC) are grouped together because their prognosis and management are similar. There are three main sub-types: squamous cell lung carcinoma, adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...

, and large-cell lung carcinoma.
style="font-size:90%;background:#E5AFAA;"|Sub-types of non-small-cell lung cancer in
smokers and never-smokers
Histological sub-type Frequency of non-small-cell lung cancers (%)
Smokers Never-smokers
Squamous cell lung carcinoma 42 33
Adenocarcinoma Adenocarcinoma (not otherwise specified) 39 35
Bronchioloalveolar carcinoma
Bronchioloalveolar carcinoma
Bronchioloalveolar carcinoma is a term describing certain variants of lung cancer arising in the distal bronchioles or alveoli that initially exhibit a specific non-invasive growth pattern.-Classification:...

4 10
Carcinoid
Carcinoid
Carcinoid is a slow-growing type of neuroendocrine tumor, originating in the cells of the neuroendocrine system.In 2000, the World Health Organization redefined "carcinoid", but this new definition has not been accepted by all practitioners. This has led to some complexity in distinguishing...

7 16
Other 8 6

Accounting for 25% of lung cancers, squamous cell lung carcinoma usually starts near a central bronchus
Bronchus
A bronchus is a passage of airway in the respiratory tract that conducts air into the lungs. The bronchus branches into smaller tubes, which in turn become bronchioles....

. A hollow cavity and associated necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

 are commonly found at the center of the tumor. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.

Adenocarcinoma accounts for 40% of non-small-cell lung cancers. It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer. A subtype of adenocarcinoma, the bronchioloalveolar carcinoma
Bronchioloalveolar carcinoma
Bronchioloalveolar carcinoma is a term describing certain variants of lung cancer arising in the distal bronchioles or alveoli that initially exhibit a specific non-invasive growth pattern.-Classification:...

, is more common in female never-smokers, and may have different responses to treatment.

Small-cell lung carcinoma

Small-cell lung carcinoma (SCLC) is less common. It was formerly referred to as "oat-cell" carcinoma. Most cases arise in the larger airways (primary and secondary bronchi
Bronchus
A bronchus is a passage of airway in the respiratory tract that conducts air into the lungs. The bronchus branches into smaller tubes, which in turn become bronchioles....

) and grow rapidly, becoming quite large. The small cells contain dense neurosecretory granules (vesicles
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...

 containing neuroendocrine hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s), which give this tumor an endocrine/paraneoplastic syndrome association. While initially more sensitive to chemotherapy and radiation, it is often metastatic at presentation, and ultimately carries a worse prognosis. Small-cell lung cancers have long been dichotomously staged into limited and extensive stage disease. This type of lung cancer is strongly associated with smoking.

Others

Lung cancers are highly heterogeneous malignancies, with tumors containing more than one subtype being very common.

Currently, the most widely recognized and utilized lung cancer classification system is the 4th revision of the Histological Typing of Lung and Pleural Tumours, published in 2004 as a cooperative effort by the World Health Organization and the International Association for the Study of Lung Cancer. It recognizes numerous other distinct histopathological entities of non-small-cell lung carcinoma, organized into several additional subtypes, including sarcomatoid carcinoma
Sarcomatoid carcinoma
Sarcomatoid carcinoma is a relatively uncommon form of cancer whose malignant cells have histological, cytological, or molecular properties of both epithelial tumors and mesenchymal tumors .-Sarcomatoid Carcinomas of the Lung:...

, salivary gland tumors
Salivary gland cancer
Salivary gland cancer is a cancer that forms in tissues of a salivary gland. The salivary glands are classified as major and minor. The major salivary glands consist of the parotid, submandibular, and sublingual glands. The minor glands include small mucus-secreting glands located throughout the...

, carcinoid tumor, and adenosquamous carcinoma
Adenosquamous carcinoma
Adenosquamous carcinoma is a type of cancer that contains two types of cells: squamous cells and gland-like cells.- External links :* entry in the public domain NCI Dictionary of Cancer Terms...

. The latter subtype includes tumors containing at least 10% each of adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...

 and squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...

. When a tumor is found to contain a mixture of both small-cell carcinoma and non-small-cell carcinoma, it is classified as a variant of small-cell carcinoma and called a combined small-cell carcinoma. Combined small-cell carcinoma is the only currently recognized variant of small-cell carcinoma.

In infants and children, the most common primary lung cancers are pleuropulmonary blastoma
Pleuropulmonary blastoma
Pleuropulmonary blastoma is a rare cancer originating in the lung or pleural cavity. It occurs most often in infants and young children but also has been reported in adults...

 and carcinoid tumor.

Metastasis

The lung is a common place for metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 of tumors from other parts of the body. Secondary cancers are classified by the site of origin; e.g., breast cancer that has spread to the lung is called breast cancer. Metastases often have a characteristic round appearance on chest radiograph. Solitary round lung nodules are not infrequently of an uncertain etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....

 and may prompt a lung biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

.

In children, the majority of lung cancers are secondary.

Primary lung cancers themselves most commonly metastasize to the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

s, liver, brain, and bone.

Staging

Lung cancer staging
Cancer staging
The stage of a cancer is a description of the extent the cancer has spread. The stage often takes into account the size of a tumor, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized to , and whether it has spread to distant organs...

 is an assessment of the degree of spread of the cancer from its original source. In most studies, it is the most important factor affecting the prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...

 and potential treatment of lung cancer.

Staging varies for the two major cell types of lung cancer (non-small cell lung carcinoma and small cell lung carcinoma). It is normally done prior to attempts at curative therapy, and usually consists of an extensive battery of tests, to include physical examination, laboratory tests, imaging studies, and/or biopsies and other invasive procedures (such as mediastinoscopy
Mediastinoscopy
Mediastinoscopy is a procedure that enables visualization of the contents of the mediastinum, usually for the purpose of obtaining a biopsy. Mediastinoscopy is often used for staging of lymph nodes of lung cancer or for diagnosing other conditions affecting structures in the mediastinum such as...

). Non-small cell lung carcinoma is usually staged from IA ("one A"; best prognosis) to IV ("four"; worst prognosis). Small cell lung carcinoma has traditionally been classified as limited stage (confined to one half of the chest and within the scope of a single tolerable radiotherapy field) or extensive stage (more widespread disease).

For both NSCLC and SCLC, there are two general types of staging evaluations:

Clinical Staging: evaluated prior to definitive surgery, and typically based on the results of physical examination, imaging studies, and pertinent laboratory findings. Does not necessarily involve a pathologist.

Pathological Staging: usually evaluated either intra- or post-operatively, and based on the combined results of surgical and clinical findings.

Prevention

Prevention is the most cost-effective means of fighting lung cancer. While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation
Smoking cessation
Smoking cessation is the process of discontinuing the practice of inhaling a smoked substance. This article focuses exclusively on cessation of tobacco smoking; however, the methods described may apply to cessation of smoking other substances that can be difficult to stop using due to the...

 is an important preventive tool in this process. Of utmost importance are prevention programs that target the young. In 1998 the Master Settlement Agreement
Master Settlement Agreement
The Tobacco Master Settlement Agreement was entered in November 1998, originally between the four largest US tobacco companies and the attorneys general of 46 states...

 entitled 46 states in the USA to an annual payout from the tobacco companies. Between the settlement money and tobacco taxes, each state's public health department funds their prevention programs, although none of the states are living up to the Center for Disease Control's recommended amount by spending 15 percent of tobacco taxes and settlement revenues on these prevention efforts.

Policy interventions to decrease passive smoking
Passive smoking
Passive smoking is the inhalation of smoke, called secondhand smoke or environmental tobacco smoke , from tobacco products used by others. It occurs when tobacco smoke permeates any environment, causing its inhalation by people within that environment. Exposure to secondhand tobacco smoke causes...

 in public areas such as restaurants and workplaces have become more common in many Western countries, with California taking a lead in banning smoking in public establishments in 1998. Ireland played a similar role in Europe in 2004, followed by Italy and Norway in 2005, Scotland as well as several others in 2006, England in 2007, France in 2008 and Turkey in 2009. New Zealand has banned smoking in public places as of 2004. The state of Bhutan
Bhutan
Bhutan , officially the Kingdom of Bhutan, is a landlocked state in South Asia, located at the eastern end of the Himalayas and bordered to the south, east and west by the Republic of India and to the north by the People's Republic of China...

 has had a complete smoking ban since 2005. In many countries, pressure groups are campaigning for similar bans. In 2007, Chandigarh
Chandigarh
Chandigarh is a union territory of India that serves as the capital of two states, Haryana and Punjab. The name Chandigarh translates as "The Fort of Chandi". The name is from an ancient temple called Chandi Mandir, devoted to the Hindu goddess Chandi, in the city...

 became the first city in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...

 to become smoke-free. India introduced a total ban on smoking in public places on 2 October 2008.

Arguments cited against such bans are criminalization
Criminalization
Criminalization or criminalisation, in criminology, is "the process by which behaviors and individuals are transformed into crime and criminals". Previously legal acts may be transformed into crimes by legislation or judicial decision...

 of smoking, increased risk of smuggling
Smuggling
Smuggling is the clandestine transportation of goods or persons, such as out of a building, into a prison, or across an international border, in violation of applicable laws or other regulations.There are various motivations to smuggle...

, and the risk that such a ban cannot be enforced.

The long-term use of supplemental multivitamins—such as vitamin C, vitamin E, and folate—does not reduce the risk of lung cancer. Indeed long-term intake of high doses of vitamin E supplements may even increase the risk of lung cancer. However, eating at least five servings of fruits and vegetables per day and following a diet that conforms to the American Cancer Society's guidelines may help lower risk.

The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where already instituted.

Screening

Screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....

 refers to the use of medical test
Medical test
A diagnostic test is any kind of medical test performed to aid in the diagnosis or detection of disease. For example:* to diagnose diseases, and preferably sub-classify it regarding, for example, severity and treatability...

s to detect disease in asymptomatic people. Possible screening tests for lung cancer include chest radiograph, or computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

 (CT). As of December 2009, screening programs for lung cancer have not demonstrated any benefit.

Treatment

Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread
Cancer staging
The stage of a cancer is a description of the extent the cancer has spread. The stage often takes into account the size of a tumor, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized to , and whether it has spread to distant organs...

, and the patient's performance status
Performance status
In medicine , performance status is an attempt to quantify cancer patients' general well-being and activities of daily life. This measure is used to determine whether they can receive chemotherapy, whether dose adjustment is necessary, and as a measure for the required intensity of palliative care...

. Common treatments include palliative care
Palliative care
Palliative care is a specialized area of healthcare that focuses on relieving and preventing the suffering of patients...

, surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

, chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

, and radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...

.

Surgery

If investigations confirm lung cancer, CT scan and often positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...

 (PET) are used to determine whether the disease is localized and amenable to surgery or whether it has spread to the point where it cannot be cured surgically.

Blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....

s and spirometry
Spirometry
Spirometry is the most common of the pulmonary function tests , measuring lung function, specifically the measurement of the amount and/or speed of air that can be inhaled and exhaled...

 (lung function testing) are also necessary to assess whether the patient is well enough to be operated on. If spirometry reveals poor respiratory reserve (often due to chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...

), surgery may be contraindicated.

Surgery for lung cancer has an operative death rate of about 4.4%, depending on the patient's lung function and other risk factors. In non-small-cell lung carcinoma, surgery is usually only an option if the cancer is limited to one lung, up to stage IIIA. This is assessed with medical imaging (computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

, positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...

). A sufficient preoperative respiratory reserve must be present to allow adequate lung function after the tissue is removed.

Procedures include wedge resection
Wedge resection (lung)
Wedge resection of the lung is a surgical operation where a part of a lung is removed. It is done to remove a localized portion of diseased lung, such as early stage lung cancer....

 (removal of part of a lobe), segmentectomy (removal of an anatomic division of a particular lobe of the lung), lobectomy
Lobectomy (lung)
Lobectomy of the lung is a surgical operation where a lobe of the lung is removed. It is done to remove a portion of diseased lung, such as early stage lung cancer.See also: Lung volume reduction surgery...

 (one lobe), bilobectomy (two lobes), or pneumonectomy
Pneumonectomy
A pneumonectomy is a surgical procedure to remove a lung. Removal of just one lobe of the lung is specifically referred to as a lobectomy, and that of a segment of the lung as a wedge resection .-Indications:...

 (whole lung). In patients with adequate respiratory reserve, lobectomy is the preferred option, as this minimizes the chance of local recurrence. If the patient does not have enough functional lung for this, wedge resection may be performed. Radioactive iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....

 brachytherapy
Brachytherapy
Brachytherapy , also known as internal radiotherapy, sealed source radiotherapy, curietherapy or endocurietherapy, is a form of radiotherapy where a radiation source is placed inside or next to the area requiring treatment...

 at the margins of wedge excision may reduce recurrence to that of lobectomy.

Video-assisted thoracoscopic surgery
Video-assisted thoracoscopic surgery
Video-assisted thoracoscopic surgery is a type of thoracic surgery performed using a small video camera that is introduced into the patient's chest via a scope. The surgeon is able to view the instruments that are being used along with the anatomy on which the surgeon is operating...

 and VATS lobectomy
VATS lobectomy
Video-assisted thoracoscopic surgery lobectomy is an approach to lung cancer surgery.-Traditional approach to lung cancer surgery: thoracotomy:Anatomic lung resection, i.e...

 have allowed for minimally invasive approaches to lung cancer surgery that may have the advantages of quicker recovery, shorter hospital stay and diminished hospital costs.

Early studies suggested that small-cell lung carcinoma (SCLC) fared better when treated with chemotherapy and/or radiation than when treated surgically. While this approach to treating SCLC remains the current standard of care, the role of surgery in SCLC is being reconsidered, recent reviews indicating that surgery might improve outcomes when added to chemotherapy and radiation in early stage SCLC and combined forms of SCLC and NSCLC.

Radiotherapy

Radiotherapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...

 is often given together with chemotherapy, and may be used with curative intent in patients with non-small-cell lung carcinoma who are not eligible for surgery. This form of high intensity radiotherapy is called radical radiotherapy. A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period. For small-cell lung carcinoma cases that are potentially curable, chest radiation is often recommended in addition to chemotherapy. The use of adjuvant thoracic radiotherapy following curative intent surgery for non-small-cell lung carcinoma is not well established and is controversial. Benefits, if any, may only be limited to those in whom the tumor has spread to the mediastinal lymph nodes.

For both non-small-cell lung carcinoma and small-cell lung carcinoma patients, smaller doses of radiation to the chest may be used for symptom control (palliative
Palliative care
Palliative care is a specialized area of healthcare that focuses on relieving and preventing the suffering of patients...

 radiotherapy). Unlike other treatments, it is possible to deliver palliative radiotherapy without confirming the histological
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...

 diagnosis of lung cancer.

Brachytherapy
Brachytherapy
Brachytherapy , also known as internal radiotherapy, sealed source radiotherapy, curietherapy or endocurietherapy, is a form of radiotherapy where a radiation source is placed inside or next to the area requiring treatment...

 (localized radiotherapy) may be given directly inside the airway when cancer affects a short section of bronchus. It is used when inoperable lung cancer causes blockage of a large airway.

Patients with limited-stage small-cell lung carcinoma are usually given prophylactic cranial irradiation (PCI). This is a type of radiotherapy to the brain, used to reduce the risk of metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

. More recently, PCI has also been shown to be beneficial in those with extensive small-cell lung cancer. In patients whose cancer has improved following a course of chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

, PCI has been shown to reduce the cumulative risk of brain metastases within one year from 40.4% to 14.6%.

Recent improvements in targeting and imaging have led to the development of extracranial stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiation therapy, very high doses are delivered in a small number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities.

Small-cell lung carcinoma

Even if relatively early stage, small-cell lung carcinoma is treated primarily with chemotherapy and radiation. In small-cell lung carcinoma, cisplatin and etoposide are most commonly used. Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan
Topotecan
Topotecan hydrochloride is a chemotherapy agent that is a topoisomerase I inhibitor. It is the water-soluble derivative of camptothecin...

, and irinotecan
Irinotecan
Irinotecan is a drug used for the treatment of cancer.Irinotecan prevents DNA from unwinding by inhibition of topoisomerase 1. In chemical terms, it is a semisynthetic analogue of the natural alkaloid camptothecin....

 are also used. Celecoxib
Celecoxib
Celecoxib INN is a sulfa non-steroidal anti-inflammatory drug and selective COX-2 inhibitor used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial...

 showed a potential signal of response in a small study.

Non-small-cell lung carcinoma

Primary chemotherapy is also given in advanced and metastatic non-small-cell lung carcinoma.

Testing for the molecular genetic subtype of non-small-cell lung cancer may be of assistance in selecting the most appropriate initial therapy For example, mutation of the epidermal growth factor receptor gene may predict whether initial treatment with a specific inhibitor or with chemotherapy is more advantageous.

Advanced non-small-cell lung carcinoma is often treated with cisplatin
Cisplatin
Cisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...

 or carboplatin
Carboplatin
Carboplatin, or cis-Diammineplatinum is a chemotherapy drug used against some forms of cancer...

, in combination with gemcitabine, paclitaxel
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...

, docetaxel, etoposide
Etoposide
Etoposide phosphate is an anti-cancer agent. It is known in the laboratory as a topoisomerase poison. Etoposide is often incorrectly referred to as a topoisomerase inhibitor in order to avoid using the term "poison" in a clinical setting...

, or vinorelbine
Vinorelbine
Vinorelbine is an anti-mitotic chemotherapy drug that is given as a treatment for some types of cancer, including breast cancer and non-small cell lung cancer.-Pharmacology:...

. Bevacizumab
Bevacizumab
Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....

 improves results in non-squamous cancers treated with paclitaxel and carboplatin in patients less than 70 years old who have reasonable general performance status.

Pemetrexed
Pemetrexed
Pemetrexed is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of Pleural Mesothelioma as well as non-small cell lung cancer.-History:...

 has been approved for use in non-small-cell lung cancer. For adenocarcinoma and large-cell lung cancer, cisplatin with pemetrexed was more beneficial than cisplatin and gemcitabine; squamous cancer had the opposite results. As a consequence, subtyping of non-small lung cancer histology has become more important.

The U.S. Food and Drug Administration (FDA) approved erlotinib
Erlotinib
Erlotinib hydrochloride is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor . It is marketed in the United States by Genentech and OSI...

 (Tarceva) for the treatment of locally advanced or metastatic non-small cell lung cancer that has failed at least one prior chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

 regimen, and has also approved its use as maintenance treatment in locally advanced or metastatic non-small cell lung cancer that has not progressed after four cycles of platinum-based first-line chemotherapy.

The U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

  approved crizotinib
Crizotinib
Crizotinib , is an ALK inhibitor, approved for treatment of some non-small cell lung carcinoma in the US, and undergoing clinical trials testing its safety and efficacy in anaplastic large cell lymphoma, neuroblastoma, and other advanced solid tumors in both adults and children.- Mechanism of...

 (Xalkori) to treat certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase
Anaplastic lymphoma kinase
Anaplastic lymphoma kinase also known as ALK tyrosine kinase receptor or CD246 is an enzyme that in humans is encoded by the ALK gene.-Function:...

 (ALK) gene.

Bronchoalveolar carcinoma is a subtype of non-small-cell lung carcinoma that may respond to gefitinib
Gefitinib
Gefitinib INN , trade name Iressa, is a drug used in the treatment of certain types of cancer, particularly those with mutated and overactive EGFR. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor in target cells...

 and erlotinib
Erlotinib
Erlotinib hydrochloride is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor . It is marketed in the United States by Genentech and OSI...

.

Maintenance therapy

In advanced non-small-cell lung cancer there are several approaches for continuing treatment after an initial response to therapy. Switch maintenance changes to different medications than the initial therapy and can use pemetrexed
Pemetrexed
Pemetrexed is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of Pleural Mesothelioma as well as non-small cell lung cancer.-History:...

, erlotinib, and docetaxel, although pemetrexed is only used in non-squamous NSCLC.

Adjuvant chemotherapy

Adjuvant chemotherapy
Adjuvant chemotherapy
Adjuvant therapy, also called adjuvant care, is treatment that is given in addition to the primary, main or initial treatment. The surgeries and complex treatment regimens used in cancer therapy have led the term to be used mainly to describe adjuvant cancer treatments...

 refers to the use of chemotherapy after apparently curative surgery to improve the outcome. In non-small-cell lung cancer, samples are taken during surgery of nearby lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

s. If these samples contain cancer, the patient has stage II or III disease. In this situation, adjuvant chemotherapy may improve survival by up to 15%. Standard practice has often been to offer platinum-based chemotherapy (including either cisplatin or carboplatin). However, the benefit of platinum-based adjuvant chemotherapy was confined to patients who had tumors with low ERCC1
ERCC1
DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ERCC1 gene.- Function :The function of the ERCC1 protein is predominantly in nucleotide excision repair of damaged DNA...

 (excision repair cross-complementing 1) activity.

Adjuvant chemotherapy for patients with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit. Trials of preoperative chemotherapy (neoadjuvant chemotherapy
Neoadjuvant chemotherapy
Neoadjuvant therapy is the administration of therapeutic agents before a main treatment. One example is neoadjuvant hormone therapy prior to radical radiotherapy for adenocarcinoma of the prostate...

) in resectable non-small-cell lung carcinoma have been inconclusive.

Interventional radiology

Radiofrequency ablation
Radiofrequency ablation
Radio frequency ablation is a medical procedure where part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from the high frequency alternating current to treat a medical disorder...

 should currently be considered an investigational technique in the treatment of bronchogenic carcinoma. It is done by inserting a small heat probe into the tumor to kill the tumor cells.

Palliative care

In a 2010 study of patients with metastatic non–small-cell lung cancer, early palliative care
Palliative care
Palliative care is a specialized area of healthcare that focuses on relieving and preventing the suffering of patients...

 led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival" (increased by 3 months).

Other studies in advanced cancer also found benefit from palliative care, or found hospice involvement to be beneficial. These approaches allow additional discussion of treatment options and provide opportunities to arrive at well-considered decisions and may avoid unhelpful but expensive care at the end of life.

Chemotherapy may be combined with palliative care in the treatment of the non-small-cell lung cancer. In advanced NSCLC, a 1994 meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...

 found that appropriate chemotherapy improved average
Median
In probability theory and statistics, a median is described as the numerical value separating the higher half of a sample, a population, or a probability distribution, from the lower half. The median of a finite list of numbers can be found by arranging all the observations from lowest value to...

 survival over supportive care alone, as well as improving quality of life. With adequate physical fitness
Performance status
In medicine , performance status is an attempt to quantify cancer patients' general well-being and activities of daily life. This measure is used to determine whether they can receive chemotherapy, whether dose adjustment is necessary, and as a measure for the required intensity of palliative care...

, maintaining chemotherapy during lung cancer palliation offers a 1.5 to 3 months prolongation of survival, symptomatic relief and an improvement in quality of life, with better results seen with modern agents. Since 2008, the NSCLC Meta-Analyses Collaborative Group has recommended that if the recipient wants and can tolerate treatment then chemotherapy should be considered in advanced NSCLC.

Prognosis

Prognostic factors in non-small-cell lung cancer include presence or absence of pulmonary symptoms, tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 size, cell type (histology
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...

), degree of spread (stage) and metastases to multiple lymph nodes, and vascular invasion. For patients with inoperable disease, prognosis is adversely affected by poor performance status
Performance status
In medicine , performance status is an attempt to quantify cancer patients' general well-being and activities of daily life. This measure is used to determine whether they can receive chemotherapy, whether dose adjustment is necessary, and as a measure for the required intensity of palliative care...

 and weight loss of more than 10%. Prognostic factors in small-cell lung cancer include performance status
Performance status
In medicine , performance status is an attempt to quantify cancer patients' general well-being and activities of daily life. This measure is used to determine whether they can receive chemotherapy, whether dose adjustment is necessary, and as a measure for the required intensity of palliative care...

, gender
Gender
Gender is a range of characteristics used to distinguish between males and females, particularly in the cases of men and women and the masculine and feminine attributes assigned to them. Depending on the context, the discriminating characteristics vary from sex to social role to gender identity...

, stage of disease, and involvement of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 or liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 at the time of diagnosis
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...

.

For non-small-cell lung carcinoma (NSCLC), prognosis is generally poor. Following complete surgical resection of stage IA disease, five-year survival is 67%. With stage IB disease, five-year survival is 57%. The five-year survival rate of patients with stage IV NSCLC is about 1%.

For small-cell lung carcinoma, prognosis is also generally poor. The overall five-year survival for patients with SCLC is about 5%. Patients with extensive-stage SCLC have an average five-year survival rate of less than 1%. The median
Median
In probability theory and statistics, a median is described as the numerical value separating the higher half of a sample, a population, or a probability distribution, from the lower half. The median of a finite list of numbers can be found by arranging all the observations from lowest value to...

 survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.

According to data provided by the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...

, the median age at diagnosis of lung cancer in the United States is 70 years, and the median age at death is 72 years.

Epidemiology

Worldwide, lung cancer is the most common cancer in terms of both incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...

 and mortality (1.1 million new cases per year and 0.95 million deaths in males and 0.51 million new cases per year and 0.43 million deaths in females). The highest rates are in Europe and North America. The population segment most likely to develop lung cancer is over-fifties who have a history of smoking. Lung cancer is the second most commonly occurring form of cancer in most Western countries, and it is the leading cancer-related cause of death. In contrast to the mortality rate in men, which began declining more than 20 years ago, women's lung cancer mortality rates have been rising over the last decades, and are just recently beginning to stabilize. The evolution of "Big Tobacco
Big Tobacco
Big Tobacco is a pejorative term often applied to the tobacco industry in general, or more particularly to the "big three" tobacco corporations in the United States: Philip Morris , Reynolds American and Lorillard...

" plays a significant role in the smoking culture. Tobacco companies have focused their efforts since the 1970s at marketing their product toward women and girls, especially with "light" and "low-tar" cigarettes. Among lifetime nonsmokers, men have higher age-standardized lung cancer death rates than women.

Not all cases of lung cancer are due to smoking, but the role of passive smoking
Passive smoking
Passive smoking is the inhalation of smoke, called secondhand smoke or environmental tobacco smoke , from tobacco products used by others. It occurs when tobacco smoke permeates any environment, causing its inhalation by people within that environment. Exposure to secondhand tobacco smoke causes...

 is increasingly being recognized as a risk factor for lung cancer—leading to policy interventions to decrease undesired exposure of nonsmokers to others' tobacco smoke. Emissions from automobiles, factories, and power plants also pose potential risks.

Eastern Europe
Eastern Europe
Eastern Europe is the eastern part of Europe. The term has widely disparate geopolitical, geographical, cultural and socioeconomic readings, which makes it highly context-dependent and even volatile, and there are "almost as many definitions of Eastern Europe as there are scholars of the region"...

 has the highest lung cancer mortality among men, while northern Europe and the U.S. have the highest mortality among women. In the United States, black men and women have a higher incidence. Lung cancer incidence is currently less common in developing countries. With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China and India.

Lung cancer incidence (by country) has an inverse correlation with sunlight
Sunlight
Sunlight, in the broad sense, is the total frequency spectrum of electromagnetic radiation given off by the Sun. On Earth, sunlight is filtered through the Earth's atmosphere, and solar radiation is obvious as daylight when the Sun is above the horizon.When the direct solar radiation is not blocked...

 and UVB
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...

 exposure. One possible explanation is a preventive effect of vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....

, which is produced in the skin on exposure to sunlight.

From the 1950s, the incidence of lung adenocarcinoma started to rise relative to other types of lung cancer. This is partly due to the introduction of filter cigarettes. The use of filters removes larger particles from tobacco smoke, thus reducing deposition in larger airways. However the smoker has to inhale more deeply to receive the same amount of nicotine, increasing particle deposition in small airways where adenocarcinoma tends to arise. The incidence of lung adenocarcinoma in the U.S. has fallen since 1999. This may be due to reduction in environmental air pollution.
However, in some developing countries like India, there has been little change in the epidemiology with squamous cell carcinoma continuing to be the predominant histological type. An absence of change in the type of tobacco smoking or the pattern of tobacco consumption in the population could be one of the possible reasons.

History

Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761. Different aspects of lung cancer were described further in 1810. Malignant lung tumors made up only 1% of all cancers seen at autopsy in 1878, but had risen to 10–15% by the early 1900s. Case reports in the medical literature numbered only 374 worldwide in 1912, but a review of autopsies showed that the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952. In Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...

 in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer, which led to an aggressive antismoking campaign
Anti-tobacco movement in Nazi Germany
After German doctors became the first to identify the link between smoking and lung cancer, Nazi Germany initiated a strong anti-tobacco movement and led the first public anti-smoking campaign in modern history...

. The British Doctors Study
British Doctors Study
The British Doctors Study is the generally accepted name of a prospective cohort study which ran from 1951 to 2001, and in 1956 provided convincing statistical proof that tobacco smoking increased the risk of lung cancer.-Context:...

, published in the 1950s, was the first solid epidemiological
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...

 evidence of the link between lung cancer and smoking. As a result, in 1964 the Surgeon General of the United States
Surgeon General of the United States
The Surgeon General of the United States is the operational head of the Public Health Service Commissioned Corps and thus the leading spokesperson on matters of public health in the federal government...

 recommended that smokers should stop smoking.

The connection with radon
Radon
Radon is a chemical element with symbol Rn and atomic number 86. It is a radioactive, colorless, odorless, tasteless noble gas, occurring naturally as the decay product of uranium or thorium. Its most stable isotope, 222Rn, has a half-life of 3.8 days...

 gas was first recognized among miners in the Ore Mountains near Schneeberg, Saxony
Schneeberg, Saxony
Schneeberg is a town in Saxony’s district of Erzgebirgskreis. It has roughly 16,400 inhabitants and belongs to the Town League of Silberberg . It lies 4 km west of Aue, and southeast of Zwickau.- Location :...

. Silver
Silver
Silver is a metallic chemical element with the chemical symbol Ag and atomic number 47. A soft, white, lustrous transition metal, it has the highest electrical conductivity of any element and the highest thermal conductivity of any metal...

 has been mined there since 1470, and these mines are rich in uranium
Uranium
Uranium is a silvery-white metallic chemical element in the actinide series of the periodic table, with atomic number 92. It is assigned the chemical symbol U. A uranium atom has 92 protons and 92 electrons, of which 6 are valence electrons...

, with its accompanying radium
Radium
Radium is a chemical element with atomic number 88, represented by the symbol Ra. Radium is an almost pure-white alkaline earth metal, but it readily oxidizes on exposure to air, becoming black in color. All isotopes of radium are highly radioactive, with the most stable isotope being radium-226,...

 and radon gas. Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s. An estimated 75% of former miners died from lung cancer. Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium.

The first successful pneumonectomy
Pneumonectomy
A pneumonectomy is a surgical procedure to remove a lung. Removal of just one lobe of the lung is specifically referred to as a lobectomy, and that of a segment of the lung as a wedge resection .-Indications:...

 for lung cancer was performed in 1933. Palliative radiotherapy has been used since the 1940s. Radical radiotherapy, initially used in the 1950s, was an attempt to use larger radiation doses in patients with relatively early stage lung cancer but who were otherwise unfit for surgery. In 1997, continuous hyperfractionated accelerated radiotherapy (CHART) was seen as an improvement over conventional radical radiotherapy.

With small-cell lung carcinoma, initial attempts in the 1960s at surgical resection and radical radiotherapy were unsuccessful. In the 1970s, successful chemotherapy regimens were developed.

External links

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