Lung cancer pathophysiology: Difference between revisions
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=== Viruses === | === Viruses === | ||
[[Virus]]es are known to cause lung cancer in animals<ref name="Leroux">{{cite journal | last =Leroux | first =C | coauthors =Girard N, Cottin V et al. | title =Jaagsiekte Sheep Retrovirus (JSRV): from virus to lung cancer in sheep |journal =Veterinary Research |volume =38 | issue =2 | pages =211–228 | date =Mar-Apr 2007 | pmid =17257570 }}</ref><ref name="Palmarini">{{cite journal | last =Palmarini | first =M | coauthors =Fan H | title =Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer| journal =Journal of the National Cancer Institute | volume =93 | issue =21 | pages =1603–1614 | publisher =Oxford University Press| date =November 2001 | url =http://jnci.oxfordjournals.org/cgi/content/full/93/21/1603 | pmid =11698564 | accessdate =2007-08-11}}</ref> and recent evidence suggests similar potential in humans. Implicated viruses include [[human papillomavirus]],<ref name="Cheng">{{cite journal | last =Cheng | first =YW | coauthors = Chiou HL, Sheu GT et al. | title =The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women | journal =Cancer Research | volume =61 | issue =7| pages =2799–2803 | publisher = American Association for Cancer Research | date =Apr 2001 | url =http://cancerres.aacrjournals.org/cgi/content/full/61/7/2799 | pmid =11306446 | accessdate =2007-08-11 }}</ref> [[JC virus]],<ref name="Zheng">{{cite journal | last =Zheng | first =H | coauthors =Aziz HA, Nakanishi Y et al. | title =Oncogenic role of JC virus in lung cancer | journal =Journal of Pathology | volume =212 | issue =3 | pages =306–315 | date =May 2007 | pmid =17534844 }}</ref>[[SV40|simian virus 40]] (SV40), [[BK virus]] and [[cytomegalovirus]].<ref name="Giuliani">{{cite journal | last =Giuliani | first =L | coauthors =Jaxmar T, Casadio C et al. | title =Detection of oncogenic viruses (SV40, BKV, JCV, HCMV, HPV) and p53 codon 72 polymorphism in lung carcinoma | journal =Lung Cancer | volume=57 | issue=3 | pages=273–281 | date =Sep 2007 | pmid =17400331}}</ref> These viruses may affect the [[cell cycle]] and inhibit [[apoptosis]], allowing uncontrolled cell division. | [[Virus]]es are known to cause lung cancer in animals<ref name="Leroux">{{cite journal | last =Leroux | first =C | coauthors =Girard N, Cottin V et al. | title =Jaagsiekte Sheep Retrovirus (JSRV): from virus to lung cancer in sheep |journal =Veterinary Research |volume =38 | issue =2 | pages =211–228 | date =Mar-Apr 2007 | pmid =17257570 }}</ref><ref name="Palmarini">{{cite journal | last =Palmarini | first =M | coauthors =Fan H | title =Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer| journal =Journal of the National Cancer Institute | volume =93 | issue =21 | pages =1603–1614 | publisher =Oxford University Press| date =November 2001 | url =http://jnci.oxfordjournals.org/cgi/content/full/93/21/1603 | pmid =11698564 | accessdate =2007-08-11}}</ref> and recent evidence suggests similar potential in humans. Implicated viruses include [[human papillomavirus]],<ref name="Cheng">{{cite journal | last =Cheng | first =YW | coauthors = Chiou HL, Sheu GT et al. | title =The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women | journal =Cancer Research | volume =61 | issue =7| pages =2799–2803 | publisher = American Association for Cancer Research | date =Apr 2001 | url =http://cancerres.aacrjournals.org/cgi/content/full/61/7/2799 | pmid =11306446 | accessdate =2007-08-11 }}</ref> [[JC virus]],<ref name="Zheng">{{cite journal | last =Zheng | first =H | coauthors =Aziz HA, Nakanishi Y et al. | title =Oncogenic role of JC virus in lung cancer | journal =Journal of Pathology | volume =212 | issue =3 | pages =306–315 | date =May 2007 | pmid =17534844 }}</ref>[[SV40|simian virus 40]] (SV40), [[BK virus]] and [[cytomegalovirus]].<ref name="Giuliani">{{cite journal | last =Giuliani | first =L | coauthors =Jaxmar T, Casadio C et al. | title =Detection of oncogenic viruses (SV40, BKV, JCV, HCMV, HPV) and p53 codon 72 polymorphism in lung carcinoma | journal =Lung Cancer | volume=57 | issue=3 | pages=273–281 | date =Sep 2007 | pmid =17400331}}</ref> These viruses may affect the [[cell cycle]] and inhibit [[apoptosis]], allowing uncontrolled cell division. | ||
===Infection and Inflammation=== | |||
New studies have shown that there may be a correlation between general inflammation of lung tissue and the development of lung cancers. One of the models that supports this idea has to do with the release of [[neutrophils]], which are released in response to bacterial infection and the initial stages of inflammation. The hypothesis is that neutrophils may activate reactive oxygen or nitrogen species which can bind to DNA, subsequently leading to genomic alterations. Based on this idea, it can be inferred that inflammation may be a cancer initiator or [[promoter]]. Also, tissue repair from inflammation is associated with cellular proliferation. During cellular proliferation there may be errors in chromosomal replication that can cause further DNA mutation. The final part of the hypothesis refers to [[angiogenesis]], which is very important in regards to the growth of tumors. These three different causes put together make for a good environment for the development of lung cancers.<ref name="Engels">Eric A Engels.11/30/11. Inflammation in the development of lung cancer:epidemiological evidence.Expert Review of Anticancer Therapy.Apr.2008.p605</ref> | |||
Because of smoking, infections, and chronic lung diseases, the lungs are very susceptible to prolonged inflammation. Some examples are [[tuberculosis]], [[asthma]], and [[pneumonia]]. | |||
==Gross Pathology Images== | ==Gross Pathology Images== | ||
Revision as of 17:18, 30 November 2011
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Kim-Son H. Nguyen, M.D., M.P.A., Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA, Cafer Zorkun, M.D., Ph.D. [2]
Overview
Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes.[1] Oncogenes are genes that are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens.[2]Mutations in the K-ras proto-oncogene are responsible for 20–30% of non-small cell lung cancers.[3] Chromosomal damage can lead to loss of heterozygosity. 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 TP53 tumor suppressor gene, located on chromosome 17p, is often affected.[4]
Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in genes coding for interleukin-1,[5] cytochrome P450,[6] apoptosis promoters such as caspase-8,[7] and DNA repair molecules such as XRCC1.[8] People with these polymorphisms are more likely to develop lung cancer after exposure to carcinogens.
The main causes of lung cancer (and cancer in general) include carcinogens (such as those in tobacco smoke), ionizing radiation, and viral infection. This exposure causes cumulative changes to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). As more tissue becomes damaged, eventually a cancer develops.
Smoking
Cigarette smoke contains over 60 known carcinogens[9] including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene.
Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue. The length of time a person smokes as well as the amount smoked 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. Across the developed world, almost 90% of lung cancer deaths are caused by smoking.[10]
In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers,[11] and that patients who smoke at the time of diagnosis have shorter survival than those who have quit.[12]
Passive smoking—the inhalation of smoke from another's smoking—is a cause of lung cancer in non-smokers. Studies from the U.S.,[13] Europe,[14] the UK,[15] and Australia[16] have consistently shown a significant increase in relative risk among those exposed to passive smoke. Recent investigation of sidestream smoke suggests it is more dangerous than direct smoke inhalation.[17]
Radon gas
Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer after smoking.[18]
Mechanism of damage[19]
- Not from Radon gas itself
- Short lived alpha decay products cause cellular damage
- Lung cancer develops mainly from decay products irradiating lung tissue
- Lung DNA is likely damaged when an alpha particle passes through it
- Alpha particles are comparatively heavy
- Since they are heavy, alpha radiation travels very short distances
- The lungs are generally the only organ the radiation can reach, therefore lung cancer is likely the only hazard of Radon
- When a particle passes through the nucleus of a cell, the DNA will likely be damaged
- DNA Damage usually in the form of a point mutation or transformation
Asbestos
Asbestos can cause a variety of lung diseases, including lung cancer. Tiny asbestos fibers are released into the air and those fibers are breathed into the lungs. The fibers become lodged in the lungs and are stuck there for an indefinite amount of time. They can eventually lead to scarring and inflammation. Also, there is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer.[20] Many asbestos related lung cancer patients also suffer from Asbestosis. Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).
Viruses
Viruses are known to cause lung cancer in animals[21][22] and recent evidence suggests similar potential in humans. Implicated viruses include human papillomavirus,[23] JC virus,[24]simian virus 40 (SV40), BK virus and cytomegalovirus.[25] These viruses may affect the cell cycle and inhibit apoptosis, allowing uncontrolled cell division.
Infection and Inflammation
New studies have shown that there may be a correlation between general inflammation of lung tissue and the development of lung cancers. One of the models that supports this idea has to do with the release of neutrophils, which are released in response to bacterial infection and the initial stages of inflammation. The hypothesis is that neutrophils may activate reactive oxygen or nitrogen species which can bind to DNA, subsequently leading to genomic alterations. Based on this idea, it can be inferred that inflammation may be a cancer initiator or promoter. Also, tissue repair from inflammation is associated with cellular proliferation. During cellular proliferation there may be errors in chromosomal replication that can cause further DNA mutation. The final part of the hypothesis refers to angiogenesis, which is very important in regards to the growth of tumors. These three different causes put together make for a good environment for the development of lung cancers.[5]
Because of smoking, infections, and chronic lung diseases, the lungs are very susceptible to prolonged inflammation. Some examples are tuberculosis, asthma, and pneumonia.
Gross Pathology Images
References
- ↑ Fong, KM (Oct 2003). "Lung cancer. 9: Molecular biology of lung cancer: clinical implications". Thorax. BMJ Publishing Group Ltd. 58 (10): 892–900. PMID 14514947. Unknown parameter
|coauthors=ignored (help) - ↑ Salgia, R (Mar 1998). "Molecular abnormalities in lung cancer". Journal of Clinical Oncology. 16 (3): 1207–1217. PMID 9508209. Unknown parameter
|coauthors=ignored (help) - ↑ Aviel-Ronen, S (Jul 2006). "K-ras mutations in non-small-cell lung carcinoma: a review". Clinical Lung Cancer. Cancer Information Group. 8 (1): 30–38. PMID 16870043. Unknown parameter
|coauthors=ignored (help) - ↑ Devereux, TR (Mar 1996). "Molecular mechanisms of lung cancer. Interaction of environmental and genetic factors". Chest. American College of Chest Physicians. 109 (Suppl. 3): 14S–19S. PMID 8598134. Retrieved 2007-08-11. Unknown parameter
|coauthors=ignored (help) - ↑ 5.0 5.1 Engels, EA (Jul 2007). "Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer". Cancer Research. American Association for Cancer Research. 67 (13): 6520–6527. PMID 17596594. Unknown parameter
|coauthors=ignored (help) - ↑ Wenzlaff, AS (Dec 2005). "CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study". Carcinogenesis. Oxford University Press. 26 (12): 2207–2212. PMID 16051642. Unknown parameter
|coauthors=ignored (help) - ↑ Son, JW (Sep 2006). "Polymorphisms in the caspase-8 gene and the risk of lung cancer". Cancer Genetics and Cytogenetics. 169 (2): 121–127. PMID 16938569. Unknown parameter
|coauthors=ignored (help) - ↑ Yin, J (May 2007). "The DNA repair gene XRCC1 and genetic susceptibility of lung cancer in a northeastern Chinese population". Lung Cancer. 56 (2): 153–160. PMID 17316890. Unknown parameter
|coauthors=ignored (help) - ↑ Hecht, S (Oct 2003). "Tobacco carcinogens, their biomarkers and tobacco-induced cancer". Nature Reviews. Cancer. Nature Publishing Group. 3 (10): 733–744. doi:10.1038/nrc1190. PMID 14570033. Retrieved 2007-08-10.
- ↑ Peto R, R (2006). Mortality from smoking in developed countries 1950–2000: Indirect estimates from National Vital Statistics. Oxford University Press. ISBN 0-19-262535-7. Retrieved 2007-08-10. Unknown parameter
|coauthors=ignored (help) - ↑ Nordquist, LT (Aug 2004). "Improved survival in never-smokers vs current smokers with primary adenocarcinoma of the lung". Chest. American College of Chest Physicians. 126 (2): 347–351. PMID 15302716. Retrieved 2007-08-10. Unknown parameter
|coauthors=ignored (help) - ↑ Tammemagi, CM (Jan 2004). "Smoking and lung cancer survival: the role of comorbidity and treatment". Chest. American College of Chest Physicians. 125 (1): 27–37. PMID 14718417. Retrieved 2007-08-10. Unknown parameter
|coauthors=ignored (help) - ↑ CDC (Dec 1986). "1986 Surgeon General's report: the health consequences of involuntary smoking". CDC. PMID 3097495. Retrieved 2007-08-10.
* National Research Council (1986). Environmental tobacco smoke: measuring exposures and assessing health effects. National Academy Press. ISBN 0-309-07456-8.
* Template:Cite paper
* California Environmental Protection Agency (1997). "Health effects of exposure to environmental tobacco smoke". Tobacco Control. 6 (4): 346–353. PMID 9583639. Retrieved 2007-08-10.
* CDC (Dec 2001). "State-specific prevalence of current cigarette smoking among adults, and policies and attitudes about secondhand smoke—United States, 2000". Morbidity and Mortality Weekly Report. CDC. 50 (49): 1101–1106. PMID 11794619. Retrieved 2007-08-10.
* Alberg, AJ (Jan 2003). "Epidemiology of lung cancer". Chest. American College of Chest Physicians. 123 (S1): 21S–49S. PMID 12527563. Retrieved 2007-08-10. Unknown parameter|coauthors=ignored (help) - ↑ Boffetta, P (Oct 1998). "Multicenter case-control study of exposure to environmental tobacco smoke and lung cancer in Europe". Journal of the National Cancer Institute. Oxford University Press. 90 (19): 1440–1450. PMID 9776409. Retrieved 2007-08-10. Unknown parameter
|coauthors=ignored (help) - ↑ "Report of the Scientific Committee on Tobacco and Health". Department of Health. Mar 1998. Retrieved 2007-07-09.
* Hackshaw, AK (Jun 1998). "Lung cancer and passive smoking". Statistical Methods in Medical Research. 7 (2): 119–136. PMID 9654638. - ↑ Template:Cite paper
- ↑ Schick, S (Dec 2005). "Philip Morris toxicological experiments with fresh sidestream smoke: more toxic than mainstream smoke". Tobacco Control. 14 (6): 396–404. PMID 16319363. Unknown parameter
|coauthors=ignored (help) - ↑ Catelinois, O (May 2006). "Lung Cancer Attributable to Indoor Radon Exposure in France: Impact of the Risk Models and Uncertainty Analysis". Environmental Health Perspectives. National Institute of Environmental Health Science. 114 (9): 1361–1366. doi:10.1289/ehp.9070. PMID 16966089. Retrieved 2007-08-10. Unknown parameter
|coauthors=ignored (help) - ↑ University of Minnesota. http://enhs.umn.edu/hazards/hazardssite/radon/radonmolaction.html#Anchor-Molecular-23240/
- ↑ O'Reilly, KM (Mar 2007). "Asbestos-related lung disease". American Family Physician. 75 (5): 683–688. PMID 17375514. Retrieved 2007-08-18. Unknown parameter
|coauthors=ignored (help) - ↑ Leroux, C (Mar–Apr 2007). "Jaagsiekte Sheep Retrovirus (JSRV): from virus to lung cancer in sheep". Veterinary Research. 38 (2): 211–228. PMID 17257570. Unknown parameter
|coauthors=ignored (help) - ↑ Palmarini, M (November 2001). "Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer". Journal of the National Cancer Institute. Oxford University Press. 93 (21): 1603–1614. PMID 11698564. Retrieved 2007-08-11. Unknown parameter
|coauthors=ignored (help) - ↑ Cheng, YW (Apr 2001). "The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women". Cancer Research. American Association for Cancer Research. 61 (7): 2799–2803. PMID 11306446. Retrieved 2007-08-11. Unknown parameter
|coauthors=ignored (help) - ↑ Zheng, H (May 2007). "Oncogenic role of JC virus in lung cancer". Journal of Pathology. 212 (3): 306–315. PMID 17534844. Unknown parameter
|coauthors=ignored (help) - ↑ Giuliani, L (Sep 2007). "Detection of oncogenic viruses (SV40, BKV, JCV, HCMV, HPV) and p53 codon 72 polymorphism in lung carcinoma". Lung Cancer. 57 (3): 273–281. PMID 17400331. Unknown parameter
|coauthors=ignored (help)