Lung cancer pathophysiology: Difference between revisions

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==Overview==
==Overview==
The pathophysiology of lung cancer includes both genetic and environmental factors. Genetic mutations, namely mutations in '''K-ras''' oncogene and '''TP53''' tumor-suppressor gene, are associated with the development of lung cancers. Environmental factors often include smoking (most important carcinogen), radon, asbestos, viral infections, and states of chronic lung inflammation, all of which may predispose to cellular damage and DNA mutations that predispose to the development of lung cancers.
The [[pathophysiology]] of lung cancer includes both [[genetic]] and environmental factors. [[Genetic mutations]], namely mutations in '''[[KRAS|K-Ras]]''' [[oncogene]] and '''[[TP53]]''' [[tumor-suppressor gene]], are associated with the development of lung cancers. Environmental factors often include [[smoking]] (most important [[carcinogen]]), [[radon]], [[asbestos]], [[viral infections]], and states of chronic [[lung]] [[inflammation]], all of which may predispose to [[cellular]] damage and [[DNA mutations]] that predispose to the development of lung cancers.


==Pathophysiology==
==Pathophysiology==
The pathophysiology of lung cancer includes both genetic and environmental factors.<ref name="KanwalDing2017">{{cite journal|last1=Kanwal|first1=Madiha|last2=Ding|first2=Xiao-Ji|last3=Cao|first3=Yi|title=Familial risk for lung cancer|journal=Oncology Letters|volume=13|issue=2|year=2017|pages=535–542|issn=1792-1074|doi=10.3892/ol.2016.5518}}</ref>
The [[pathophysiology]] of lung cancer includes both [[genetic]] and environmental factors.<ref name="KanwalDing2017">{{cite journal|last1=Kanwal|first1=Madiha|last2=Ding|first2=Xiao-Ji|last3=Cao|first3=Yi|title=Familial risk for lung cancer|journal=Oncology Letters|volume=13|issue=2|year=2017|pages=535–542|issn=1792-1074|doi=10.3892/ol.2016.5518}}</ref>


==Genetics==
==Genetics==
*Lung cancer is initiated by activation of [[oncogene]]s or inactivation of [[tumor suppressor gene]]s.<ref name="Fong">{{cite journal | last =Fong | first =KM | coauthors = Sekido Y, Gazdar AF, Minna JD | title =Lung cancer. 9: Molecular biology of lung cancer: clinical implications | journal =Thorax | volume =58 | issue =10 | pages =892–900 | publisher = BMJ Publishing Group Ltd. | date =Oct 2003 | pmid =14514947 }}</ref>  
*Lung cancer is initiated by activation of [[oncogene]]s or inactivation of [[tumor suppressor gene]]s.<ref name="Fong">{{cite journal | last =Fong | first =KM | coauthors = Sekido Y, Gazdar AF, Minna JD | title =Lung cancer. 9: Molecular biology of lung cancer: clinical implications | journal =Thorax | volume =58 | issue =10 | pages =892–900 | publisher = BMJ Publishing Group Ltd. | date =Oct 2003 | pmid =14514947 }}</ref>  
*[[Mutation]]s in the ''[[Ras|K-ras]]'' proto-oncogene are responsible for 20% to 30% of non-small cell lung cancer cases.<ref name="Aviel-Ronen">{{cite journal | last =Aviel-Ronen | first =S | coauthors = Blackhall FH, Shepherd FA, Tsao MS | title =K-ras mutations in non-small-cell lung carcinoma: a review | journal =Clinical Lung Cancer | volume =8 | issue =1 | pages =30–38 |publisher =Cancer Information Group | date =Jul 2006 | pmid =16870043 }}</ref><ref name="pmid23122493">{{cite journal |vauthors=Karachaliou N, Mayo C, Costa C, Magrí I, Gimenez-Capitan A, Molina-Vila MA, Rosell R |title=KRAS mutations in lung cancer |journal=Clin Lung Cancer |volume=14 |issue=3 |pages=205–14 |year=2013 |pmid=23122493 |doi=10.1016/j.cllc.2012.09.007 |url=}}</ref>
*[[Mutation]]s in the ''[[Ras|K-ras]]'' [[proto-oncogene]] are responsible for 20% to 30% of non-small cell lung cancer cases.<ref name="Aviel-Ronen">{{cite journal | last =Aviel-Ronen | first =S | coauthors = Blackhall FH, Shepherd FA, Tsao MS | title =K-ras mutations in non-small-cell lung carcinoma: a review | journal =Clinical Lung Cancer | volume =8 | issue =1 | pages =30–38 |publisher =Cancer Information Group | date =Jul 2006 | pmid =16870043 }}</ref><ref name="pmid23122493">{{cite journal |vauthors=Karachaliou N, Mayo C, Costa C, Magrí I, Gimenez-Capitan A, Molina-Vila MA, Rosell R |title=KRAS mutations in lung cancer |journal=Clin Lung Cancer |volume=14 |issue=3 |pages=205–14 |year=2013 |pmid=23122493 |doi=10.1016/j.cllc.2012.09.007 |url=}}</ref>
*[[Chromosome|Chromosomal]] damage may also result in [[loss of heterozygosity]], which subsequently leads to the inactivation of tumor suppressor genes.   
*[[Chromosome|Chromosomal]] damage may also result in [[loss of heterozygosity]], which subsequently leads to the inactivation of [[tumor suppressor genes]].   
*Damage to the following chromosomes are particularly common in small cell lung carcinoma:
*Damage to the following [[chromosomes]] are particularly common in small cell lung carcinoma:
**[[Chromosome 3|Chromosome 3p]]
**[[Chromosome 3|Chromosome 3p]]
**[[Chromosome 5 (human)|Chromosome 5q]]
**[[Chromosome 5 (human)|Chromosome 5q]]
**[[Chromosome 13|Chromosome 13q]]
**[[Chromosome 13|Chromosome 13q]]
**[[Chromosome 17 (human)|Chromosome 17p]]
**[[Chromosome 17 (human)|Chromosome 17p]]
*The ''[[TP53]]'' tumor suppressor gene, located on chromosome 17p, is often mutated in lung cancers.<ref name="Devereux">{{cite journal | last =Devereux | first =TR | coauthors = Taylor JA, Barrett JC | title =Molecular mechanisms of lung cancer. Interaction of environmental and genetic factors | journal =Chest | volume =109 | issue =Suppl. 3 | pages =14S-19S | publisher =American College of Chest Physicians | date =Mar 1996 | url =http://www.chestjournal.org/cgi/reprint/109/3/14S| pmid =8598134 | accessdate =2007-08-11 }}</ref>
*The ''[[TP53]]'' [[tumor suppressor gene]], located on [[chromosome]] 17p, is often [[mutated]] in lung cancers.<ref name="Devereux">{{cite journal | last =Devereux | first =TR | coauthors = Taylor JA, Barrett JC | title =Molecular mechanisms of lung cancer. Interaction of environmental and genetic factors | journal =Chest | volume =109 | issue =Suppl. 3 | pages =14S-19S | publisher =American College of Chest Physicians | date =Mar 1996 | url =http://www.chestjournal.org/cgi/reprint/109/3/14S| pmid =8598134 | accessdate =2007-08-11 }}</ref>
*Several [[genetic polymorphism]]s are associated with lung cancer. These include polymorphisms in [[gene]]s coding for:<ref name="Engels">{{cite journal | last =Engels | first =EA | coauthors =Wu X, Gu J et al. | title =Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer | journal =Cancer Research | volume =67 | issue =13 | pages =6520–6527 | publisher =American Association for Cancer Research | date =Jul 2007 | pmid =17596594 }}</ref><ref name="Wenzlaff">{{cite journal | last =Wenzlaff | first =AS | coauthors =Cote ML, Bock CH et al. | title =CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study | journal =Carcinogenesis | volume =26 |issue =12 | pages =2207–2212 | publisher =Oxford University Press | date =Dec 2005 | pmid =16051642 }}</ref><ref name="Son">{{cite journal | last =Son | first =JW | coauthors =Kang HK, Chae MH et al. | title =Polymorphisms in the caspase-8 gene and the risk of lung cancer | journal =Cancer Genetics and Cytogenetics | volume =169 | issue =2 | pages =121–127 | date =Sep 2006 | pmid =16938569 }}</ref><ref name="Yin">{{cite journal | last =Yin | first =J | coauthors =Vogel U, Ma Y et al. | title =The DNA repair gene XRCC1 and genetic susceptibility of lung cancer in a northeastern Chinese population | journal =Lung Cancer | volume =56 | issue =2 | pages =153–160 | date =May 2007 |pmid =17316890 }}</ref>   
*Several [[genetic polymorphism]]s are associated with lung cancer. These include [[polymorphisms]] in [[gene]]s coding for:<ref name="Engels">{{cite journal | last =Engels | first =EA | coauthors =Wu X, Gu J et al. | title =Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer | journal =Cancer Research | volume =67 | issue =13 | pages =6520–6527 | publisher =American Association for Cancer Research | date =Jul 2007 | pmid =17596594 }}</ref><ref name="Wenzlaff">{{cite journal | last =Wenzlaff | first =AS | coauthors =Cote ML, Bock CH et al. | title =CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study | journal =Carcinogenesis | volume =26 |issue =12 | pages =2207–2212 | publisher =Oxford University Press | date =Dec 2005 | pmid =16051642 }}</ref><ref name="Son">{{cite journal | last =Son | first =JW | coauthors =Kang HK, Chae MH et al. | title =Polymorphisms in the caspase-8 gene and the risk of lung cancer | journal =Cancer Genetics and Cytogenetics | volume =169 | issue =2 | pages =121–127 | date =Sep 2006 | pmid =16938569 }}</ref><ref name="Yin">{{cite journal | last =Yin | first =J | coauthors =Vogel U, Ma Y et al. | title =The DNA repair gene XRCC1 and genetic susceptibility of lung cancer in a northeastern Chinese population | journal =Lung Cancer | volume =56 | issue =2 | pages =153–160 | date =May 2007 |pmid =17316890 }}</ref>   
**[[Interleukin 1|Interleukin-1]]
**[[Interleukin 1|Interleukin-1]]
**[[Cytochrome P450]]  
**[[Cytochrome P450]]  
**[[caspase]]-8, an [[apoptosis]] promoter  
**[[caspase]]-8, an [[apoptosis]] promoter  
**[[XRCC1]], a DNA repair molecule
**[[XRCC1]], a [[DNA]] repair molecule
*Individuals with these polymorphisms are thought to be more likely to develop lung cancer following exposure to [[Carcinogen|carcinogens]].
*Individuals with these [[polymorphisms]] are thought to be more likely to develop lung cancer following exposure to [[Carcinogen|carcinogens]].


==Environment==
==Environment==
Although genetics play a significant role in the pathogenesis of lung cancer, it is thought that exposure to environmental risk factors plays an equally improtant role in the development of lung cancer. The main causes of lung cancer include [[carcinogen]]s (such as those present in tobacco smoke), [[ionizing radiation]], and [[virus (biology)|viral]] infections. Chronic exposure results in cumulative alterations to the [[DNA]] in the tissue lining the [[bronchi]] of the lungs (the bronchial [[epithelium]]). Irreversible DNA changes following exposure to carcinogens are directly associated with the development of lung cancer.<ref name="pmid22054876">{{cite journal |vauthors=Dela Cruz CS, Tanoue LT, Matthay RA |title=Lung cancer: epidemiology, etiology, and prevention |journal=Clin. Chest Med. |volume=32 |issue=4 |pages=605–44 |year=2011 |pmid=22054876 |pmc=3864624 |doi=10.1016/j.ccm.2011.09.001 |url=}}</ref>
Although genetics play a significant role in the [[pathogenesis]] of lung cancer, it is thought that exposure to environmental risk factors plays an equally improtant role in the development of lung cancer. The main causes of lung cancer include [[carcinogen]]s (such as those present in tobacco smoke), [[ionizing radiation]], and [[virus (biology)|viral]] infections. Chronic exposure results in cumulative alterations to the [[DNA]] in the tissue lining the [[bronchi]] of the lungs (the [[bronchial]] [[epithelium]]). Irreversible [[DNA]] changes following exposure to [[carcinogens]] are directly associated with the development of lung cancer.<ref name="pmid22054876">{{cite journal |vauthors=Dela Cruz CS, Tanoue LT, Matthay RA |title=Lung cancer: epidemiology, etiology, and prevention |journal=Clin. Chest Med. |volume=32 |issue=4 |pages=605–44 |year=2011 |pmid=22054876 |pmc=3864624 |doi=10.1016/j.ccm.2011.09.001 |url=}}</ref>


===Smoking===
===Smoking===
*Cigarette smoking is a leading cause of lung cancer:<ref name="pmid10413421">{{cite journal |vauthors=Hecht SS |title=Tobacco smoke carcinogens and lung cancer |journal=J. Natl. Cancer Inst. |volume=91 |issue=14 |pages=1194–210 |year=1999 |pmid=10413421 |doi= |url=}}</ref><ref>Kluger, R. (1996). Ashes to ashes: America's hundred-year cigarette war, the public health, and the unabashed triumph of Philip Morris. New York: Alfred A. Knopf.</ref><ref>{{cite book | last = Proctor | first = Robert | title = The Nazi war on cancer | publisher = Princeton University Press | location = Princeton, N.J. Oxford | year = 2000 | isbn = 978-0691070513 }}</ref><ref name="Morabia2012">{{cite journal|last1=Morabia|first1=Alfredo|title=Quality, originality, and significance of the 1939 “Tobacco consumption and lung carcinoma” article by Mueller, including translation of a section of the paper|journal=Preventive Medicine|volume=55|issue=3|year=2012|pages=171–177|issn=00917435|doi=10.1016/j.ypmed.2012.05.008}}</ref><ref>Mueller F. Tabakmissbrauch und Lungencarcinom. Z. Krebsforsch. 1939;49:57–85.</ref><ref>Wynder, E. L. (1994). Prevention and cessation of tobacco use: Obstacles and challenges. J. Smoking-Related Dis. 5(Suppl. 1), 3–8.</ref><ref>Hanspeter Witschi ITEH and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616</ref><ref name="Hecht">{{cite journal | last =Hecht | first =S | title =Tobacco carcinogens, their biomarkers and tobacco-induced cancer | journal =Nature Reviews. Cancer | volume =3 | issue =10 | pages =733–744 | publisher =Nature Publishing Group | date =Oct 2003 | url =http://www.nature.com/nrc/journal/v3/n10/abs/nrc1190_fs.html;jsessionid=A78B217DFCAD36DD965F2DBA685CF121 | doi =10.1038/nrc1190 |pmid =14570033 | accessdate =2007-08-10 }}</ref><ref name="Nordquist">{{cite journal | last =Nordquist | first =LT | authorlink = | coauthors =Simon GR, Cantor A et al. | title =Improved survival in never-smokers vs current smokers with primary adenocarcinoma of the lung | journal =Chest | volume =126 | issue =2 | pages =347–351| publisher = American College of Chest Physicians | date =Aug 2004 | url =http://www.chestjournal.org/cgi/content/full/126/2/347 |pmid =15302716 | accessdate =2007-08-10 }}</ref><ref name="Peto">{{cite book | last = Peto R | first = R | coauthors = Lopez AD, Boreham J et al. | title = Mortality from smoking in developed countries 1950–2000: Indirect estimates from National Vital Statistics | publisher = Oxford University Press | date = 2006 | url=http://www.ctsu.ox.ac.uk/~tobacco/ | id = ISBN 0-19-262535-7 |accessdate =2007-08-10 }}</ref>
*[[Cigarette]] smoking is a leading cause of lung cancer:<ref name="pmid10413421">{{cite journal |vauthors=Hecht SS |title=Tobacco smoke carcinogens and lung cancer |journal=J. Natl. Cancer Inst. |volume=91 |issue=14 |pages=1194–210 |year=1999 |pmid=10413421 |doi= |url=}}</ref><ref>Kluger, R. (1996). Ashes to ashes: America's hundred-year cigarette war, the public health, and the unabashed triumph of Philip Morris. New York: Alfred A. Knopf.</ref><ref>{{cite book | last = Proctor | first = Robert | title = The Nazi war on cancer | publisher = Princeton University Press | location = Princeton, N.J. Oxford | year = 2000 | isbn = 978-0691070513 }}</ref><ref name="Morabia2012">{{cite journal|last1=Morabia|first1=Alfredo|title=Quality, originality, and significance of the 1939 “Tobacco consumption and lung carcinoma” article by Mueller, including translation of a section of the paper|journal=Preventive Medicine|volume=55|issue=3|year=2012|pages=171–177|issn=00917435|doi=10.1016/j.ypmed.2012.05.008}}</ref><ref>Mueller F. Tabakmissbrauch und Lungencarcinom. Z. Krebsforsch. 1939;49:57–85.</ref><ref>Wynder, E. L. (1994). Prevention and cessation of tobacco use: Obstacles and challenges. J. Smoking-Related Dis. 5(Suppl. 1), 3–8.</ref><ref>Hanspeter Witschi ITEH and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616</ref><ref name="Hecht">{{cite journal | last =Hecht | first =S | title =Tobacco carcinogens, their biomarkers and tobacco-induced cancer | journal =Nature Reviews. Cancer | volume =3 | issue =10 | pages =733–744 | publisher =Nature Publishing Group | date =Oct 2003 | url =http://www.nature.com/nrc/journal/v3/n10/abs/nrc1190_fs.html;jsessionid=A78B217DFCAD36DD965F2DBA685CF121 | doi =10.1038/nrc1190 |pmid =14570033 | accessdate =2007-08-10 }}</ref><ref name="Nordquist">{{cite journal | last =Nordquist | first =LT | authorlink = | coauthors =Simon GR, Cantor A et al. | title =Improved survival in never-smokers vs current smokers with primary adenocarcinoma of the lung | journal =Chest | volume =126 | issue =2 | pages =347–351| publisher = American College of Chest Physicians | date =Aug 2004 | url =http://www.chestjournal.org/cgi/content/full/126/2/347 |pmid =15302716 | accessdate =2007-08-10 }}</ref><ref name="Peto">{{cite book | last = Peto R | first = R | coauthors = Lopez AD, Boreham J et al. | title = Mortality from smoking in developed countries 1950–2000: Indirect estimates from National Vital Statistics | publisher = Oxford University Press | date = 2006 | url=http://www.ctsu.ox.ac.uk/~tobacco/ | id = ISBN 0-19-262535-7 |accessdate =2007-08-10 }}</ref>
*Cigarette smoke contains over 60 known carcinogens including [[radioisotopes]] from the [[radon]] decay sequence, [[nitrosamine]], and [[benzopyrene]].  
*[[Cigarette]] smoke contains over 60 known carcinogens including [[radioisotopes]] from the [[radon]] decay sequence, [[nitrosamine]], and [[benzopyrene]].  
*Nicotine is thought to reduce the immune response to malignant growths in exposed tissue. The length of time an individual smokes, as well as the amount, significantly increases the person's chance of developing lung cancer.
*[[Nicotine]] is thought to reduce the [[immune response]] to [[malignant]] growths in exposed tissue. The length of time an individual smokes, as well as the amount, significantly increases the person's chance of developing lung cancer.
*Among individuals who stopped smoking, the risk of lung cancer steadily decreases as lung tissue repairs itself and as contaminant particles are eliminated from the lungs. Nonetheless, it is thought that the risk of lung cancer among ever-smokers (even when stopped) is always higher than those who never smoked.
*Among individuals who stopped [[smoking]], the risk of lung cancer steadily decreases as [[lung]] [[Tissue (biology)|tissue]] repairs itself and as contaminant particles are eliminated from the [[lungs]]. Nonetheless, it is thought that the risk of lung cancer among persons with a history of [[smoking]] (even when stopped) is always higher than those who never [[Smoke|smoked]].


===Radon gas===
===Radon gas===
The association of radon gas exposure to lung cancer is described below:<ref name="Catelinois">{{cite journal | last =Catelinois | first =O | coauthors = Rogel A, Laurier D et al. | title =Lung Cancer Attributable to Indoor Radon Exposure in France: Impact of the Risk Models and Uncertainty Analysis | journal =Environmental Health Perspectives | volume =114 |issue =9 | pages =1361–1366 | publisher =National Institute of Environmental Health Science | date =May 2006 | url =http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16966089 | doi =10.1289/ehp.9070 | pmid =16966089 |accessdate =2007-08-10 }}</ref><ref name="radon">University of Minnesota.http://enhs.umn.edu/hazards/hazardssite/radon/radonmolaction.html#Anchor-Molecular-23240/</ref>
The association of [[radon]] gas exposure to lung cancer is described below:<ref name="Catelinois">{{cite journal | last =Catelinois | first =O | coauthors = Rogel A, Laurier D et al. | title =Lung Cancer Attributable to Indoor Radon Exposure in France: Impact of the Risk Models and Uncertainty Analysis | journal =Environmental Health Perspectives | volume =114 |issue =9 | pages =1361–1366 | publisher =National Institute of Environmental Health Science | date =May 2006 | url =http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16966089 | doi =10.1289/ehp.9070 | pmid =16966089 |accessdate =2007-08-10 }}</ref><ref name="radon">University of Minnesota.http://enhs.umn.edu/hazards/hazardssite/radon/radonmolaction.html#Anchor-Molecular-23240/</ref>
*[[Radon]] is a colorless and odorless [[gas]] generated by the breakdown of radioactive [[radium]] (decay product of [[uranium]]) found in the earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous.
*[[Radon]] is a colorless and odorless [[gas]] generated by the breakdown of [[radioactive]] [[radium]] (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 following smoking.
*[[Radon]] exposure is the second major cause of lung cancer following [[smoking]].
*The mechanism of lung damage following radon exposure is not thought to be due to the radon gas itself, but due to the short-lived alpha decay products that cause cellular damage and DNA mutations.
*The mechanism of lung damage following radon exposure is not thought to be due to the [[radon]] gas itself, but due to the short-lived alpha decay products that cause cellular damage and [[DNA]] [[mutations]].


===Asbestos===
===Asbestos===
*[[Asbestos]] exposure is associated with many lung diseases, including lung cancer.<ref name="JärvholmÅström2014">{{cite journal|last1=Järvholm|first1=Bengt|last2=Åström|first2=Evelina|title=The Risk of Lung Cancer After Cessation of Asbestos Exposure in Construction Workers Using Pleural Malignant Mesothelioma as a Marker of Exposure|journal=Journal of Occupational and Environmental Medicine|volume=56|issue=12|year=2014|pages=1297–1301|issn=1076-2752|doi=10.1097/JOM.0000000000000258}}</ref>
*[[Asbestos]] exposure is associated with many lung diseases, including lung cancer.<ref name="JärvholmÅström2014">{{cite journal|last1=Järvholm|first1=Bengt|last2=Åström|first2=Evelina|title=The Risk of Lung Cancer After Cessation of Asbestos Exposure in Construction Workers Using Pleural Malignant Mesothelioma as a Marker of Exposure|journal=Journal of Occupational and Environmental Medicine|volume=56|issue=12|year=2014|pages=1297–1301|issn=1076-2752|doi=10.1097/JOM.0000000000000258}}</ref>
*Tiny asbestos fibers are released into the air are breathed into the lungs. The fibers become lodged in the lungs and are stuck for an indefinite amount of time. They can eventually lead to scarring and inflammation.  
*Tiny [[asbestos]] fibers are released into the air are breathed into the [[lungs]]. The fibers become lodged in the [[lungs]] and are stuck for an indefinite amount of time. They can eventually lead to scarring and [[inflammation]].  


=== Viruses ===
=== Viruses ===
Line 54: Line 54:
**[[Cytomegalovirus]]
**[[Cytomegalovirus]]
**[[HIV]]
**[[HIV]]
*These viruses may affect the [[cell cycle]] and inhibit [[apoptosis]], allowing uncontrolled cell division.
*These [[viruses]] may affect the [[cell cycle]] and inhibit [[apoptosis]], allowing uncontrolled [[cell division]].
*[[HIV]] has also been thought to increase the risk of developing lung cancer. Although the mechanism is unknown, HIV is thought to be associated with a state of chronic lung inflammation that may potentiate cellular damage and DNA mutations.
*[[HIV]] has also been thought to increase the risk of developing lung cancer. Although the mechanism is unknown, [[HIV]] is thought to be associated with a state of chronic [[lung]] [[inflammation]] that may potentiate [[cellular]] damage and [[DNA mutations]].


===Infection and Inflammation===
===Infection and Inflammation===
*There may be a correlation between general inflammation of lung tissue and the development of lung cancers.<ref name="Engels 2" />
*There may be a correlation between general [[inflammation]] of lung tissue and the development of lung cancers.<ref name="Engels 2" />
*[[Neutrophils]] are released in response to bacterial infection and are considered to be the initial responders during inflammation.
*[[Neutrophils]] are released in response to [[bacterial]] infection and are considered to be the initial responders during [[inflammation]].
*The hypothesis is that neutrophils may activate reactive oxygen or nitrogen species, which can bind to DNA and lead to genomic alterations. Accordingly, inflammation may be thought of as an initiator or [[promoter]] of lung cancer development. 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 hypothesis is that [[neutrophils]] may activate [[Reactive oxygen species|reactive oxygen]] or [[nitrogen]] species, which can bind to [[DNA]] and lead to [[genomic]] alterations. Accordingly, [[inflammation]] may be thought of as an initiator or [[promoter]] of lung cancer development. Also, tissue repair from [[inflammation]] is associated with [[cellular]] [[Cell growth|proliferation]]. During [[cellular]] [[proliferation]] there may be errors in [[chromosomal]] [[replication]] that can cause further [[DNA mutations|DNA mutation]].  
*[[Angiogenesis]], a significant process during tumor growth, may be promoted by chronic states of inflammation, which often require increased blood flow to sites of inflammation.
*[[Angiogenesis]], a significant process during tumor growth, may be promoted by chronic states of [[inflammation]], which often require increased [[blood flow]] to sites of [[inflammation]].


===Gross Pathology===
===Gross Pathology===

Revision as of 16:39, 27 March 2018

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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. Cafer Zorkun, M.D., Ph.D. [2] Dildar Hussain, MBBS [3]Assistant Editor(s)-In-Chief: Michael Maddaleni, B.S.

Overview

The pathophysiology of lung cancer includes both genetic and environmental factors. Genetic mutations, namely mutations in K-Ras oncogene and TP53 tumor-suppressor gene, are associated with the development of lung cancers. Environmental factors often include smoking (most important carcinogen), radon, asbestos, viral infections, and states of chronic lung inflammation, all of which may predispose to cellular damage and DNA mutations that predispose to the development of lung cancers.

Pathophysiology

The pathophysiology of lung cancer includes both genetic and environmental factors.[1]

Genetics

Environment

Although genetics play a significant role in the pathogenesis of lung cancer, it is thought that exposure to environmental risk factors plays an equally improtant role in the development of lung cancer. The main causes of lung cancer include carcinogens (such as those present in tobacco smoke), ionizing radiation, and viral infections. Chronic exposure results in cumulative alterations to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). Irreversible DNA changes following exposure to carcinogens are directly associated with the development of lung cancer.[10]

Smoking

Radon gas

The association of radon gas exposure to lung cancer is described below:[21][22]

  • Radon is a colorless and odorless gas generated by the breakdown of radioactive radium (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 following smoking.
  • The mechanism of lung damage following radon exposure is not thought to be due to the radon gas itself, but due to the short-lived alpha decay products that cause cellular damage and DNA mutations.

Asbestos

  • Asbestos exposure is associated with many lung diseases, including lung cancer.[23]
  • Tiny asbestos fibers are released into the air are breathed into the lungs. The fibers become lodged in the lungs and are stuck for an indefinite amount of time. They can eventually lead to scarring and inflammation.

Viruses

Infection and Inflammation

Gross Pathology

Cross section of a human lung. The white area in the upper lobe is cancer; the black areas indicate the patient was a smoker


Microscopic Pathology

Small cell lung carcinoma (microscopic view of a core needle biopsy)


References

  1. ↑ Kanwal, Madiha; Ding, Xiao-Ji; Cao, Yi (2017). "Familial risk for lung cancer". Oncology Letters. 13 (2): 535–542. doi:10.3892/ol.2016.5518. ISSN 1792-1074.
  2. ↑ 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)
  3. ↑ 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)
  4. ↑ Karachaliou N, Mayo C, Costa C, Magrí I, Gimenez-Capitan A, Molina-Vila MA, Rosell R (2013). "KRAS mutations in lung cancer". Clin Lung Cancer. 14 (3): 205–14. doi:10.1016/j.cllc.2012.09.007. PMID 23122493.
  5. ↑ 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)
  6. ↑ 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)
  7. ↑ 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)
  8. ↑ 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)
  9. ↑ 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)
  10. ↑ Dela Cruz CS, Tanoue LT, Matthay RA (2011). "Lung cancer: epidemiology, etiology, and prevention". Clin. Chest Med. 32 (4): 605–44. doi:10.1016/j.ccm.2011.09.001. PMC 3864624. PMID 22054876.
  11. ↑ Hecht SS (1999). "Tobacco smoke carcinogens and lung cancer". J. Natl. Cancer Inst. 91 (14): 1194–210. PMID 10413421.
  12. ↑ Kluger, R. (1996). Ashes to ashes: America's hundred-year cigarette war, the public health, and the unabashed triumph of Philip Morris. New York: Alfred A. Knopf.
  13. ↑ Proctor, Robert (2000). The Nazi war on cancer. Princeton, N.J. Oxford: Princeton University Press. ISBN 978-0691070513.
  14. ↑ Morabia, Alfredo (2012). "Quality, originality, and significance of the 1939 "Tobacco consumption and lung carcinoma" article by Mueller, including translation of a section of the paper". Preventive Medicine. 55 (3): 171–177. doi:10.1016/j.ypmed.2012.05.008. ISSN 0091-7435.
  15. ↑ Mueller F. Tabakmissbrauch und Lungencarcinom. Z. Krebsforsch. 1939;49:57–85.
  16. ↑ Wynder, E. L. (1994). Prevention and cessation of tobacco use: Obstacles and challenges. J. Smoking-Related Dis. 5(Suppl. 1), 3–8.
  17. ↑ Hanspeter Witschi ITEH and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616
  18. ↑ 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.
  19. ↑ 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)
  20. ↑ 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)
  21. ↑ 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)
  22. ↑ University of Minnesota.http://enhs.umn.edu/hazards/hazardssite/radon/radonmolaction.html#Anchor-Molecular-23240/
  23. ↑ Järvholm, Bengt; Åström, Evelina (2014). "The Risk of Lung Cancer After Cessation of Asbestos Exposure in Construction Workers Using Pleural Malignant Mesothelioma as a Marker of Exposure". Journal of Occupational and Environmental Medicine. 56 (12): 1297–1301. doi:10.1097/JOM.0000000000000258. ISSN 1076-2752.
  24. ↑ 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)
  25. ↑ 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)
  26. ↑ 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)
  27. ↑ 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)
  28. ↑ 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)
  29. ↑ 29.0 29.1 Eric A Engels.11/30/11. Inflammation in the development of lung cancer:epidemiological evidence.Expert Review of Anticancer Therapy.Apr.2008.p605

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