Lung cancer pathophysiology: Difference between revisions

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** [[Tumor|Tumors]] of organs such as [[Skin cancer|skin]], [[lung]] and [[Colorectal cancer|colon]] are developed through a process called [[Tumorigenesis|multistep tumorigenesis]].
** [[Tumor|Tumors]] of organs such as [[Skin cancer|skin]], [[lung]] and [[Colorectal cancer|colon]] are developed through a process called [[Tumorigenesis|multistep tumorigenesis]].
** As with other epithelial malignancies, lung cancers are believed to arise from preneoplastic or precursor lesions in the respiratory mucosa.
** As with other epithelial malignancies, lung cancers are believed to arise from preneoplastic or precursor lesions in the respiratory mucosa.
** [[Tumorigenesis|Multistep tumorigenesis]] is development of [[tumor]] through a series of progressive pathologic events such as [[Precancerous|preneoplastic]] or [[Precursor|precursor lesions]] with corresponding [[genetic]] and [[Epigenetic|epigenetic aberrations]].
** [[Tumorigenesis|Multistep tumorigenesis]] is development of [[tumor]] through a series of progressive [[Pathological|pathologic]] events such as [[Precancerous|preneoplastic]] or [[Precursor|precursor lesions]] with corresponding [[genetic]] and [[Epigenetic|epigenetic aberrations]].
** [[Hyperplasia]], [[squamous metaplasia]], [[Dysplasia|squamous dysplasia]], and [[Carcinoma in situ|carcinoma ''in situ'' (CIS)]] comprise changes in the [[Bronchus|large airways]] that precede or accompany invasive [[squamous cell carcinoma of the lung]].<ref name="pmid18039118">{{cite journal |vauthors=Wistuba II, Gazdar AF |title=Lung cancer preneoplasia |journal=Annu Rev Pathol |volume=1 |issue= |pages=331–48 |date=2006 |pmid=18039118 |doi=10.1146/annurev.pathol.1.110304.100103 |url=}}</ref>
** [[Hyperplasia]], [[squamous metaplasia]], [[Dysplasia|squamous dysplasia]], and [[Carcinoma in situ|carcinoma ''in situ'' (CIS)]] comprise changes in the [[Bronchus|large airways]] that precede or accompany [[squamous cell carcinoma of the lung|invasive squamous cell carcinoma of the lung]].<ref name="pmid18039118">{{cite journal |vauthors=Wistuba II, Gazdar AF |title=Lung cancer preneoplasia |journal=Annu Rev Pathol |volume=1 |issue= |pages=331–48 |date=2006 |pmid=18039118 |doi=10.1146/annurev.pathol.1.110304.100103 |url=}}</ref>
** Multistep tumorigenesis explains pathogenesis of centrally located squamous cell carcinoma of the lung very well but fails to explain pathogenesis of [[Large cell carcinoma of the lung|large cell lung carcinomas]], [[Adenocarcinoma of the lung|lung adenocarcinomas]], and [[small cell lung cancer]].
** Multistep [[tumorigenesis]] explains [[pathogenesis]] of centrally located [[squamous cell carcinoma of the lung]] very well but fails to explain [[pathogenesis]] of [[Large cell carcinoma of the lung|large cell lung carcinomas]], [[Adenocarcinoma of the lung|lung adenocarcinomas]], and [[small cell lung cancer]].


* '''Accumulation of molecular abnormalities:'''
* '''Accumulation of molecular abnormalities:'''
** Another theory for pathogenesis of lung cancer is the accumulation of molecular abnormalities beyond a certain threshold point, rather than the sequence of alterations.
** Another theory for [[pathogenesis]] of lung cancer is the accumulation of [[Molecule|molecular]] abnormalities beyond a certain threshold point, rather than the sequence of alterations.
** There are no known [[Precancerous|preneoplastic lesions]] for the most common type of [[Carcinoid syndrome|neuroendocrine lung tumors]], [[Small cell lung cancer|small cell carcinoma of the lung]],  
** There are no known [[Precancerous|preneoplastic lesions]] for the most common type of [[Carcinoid syndrome|neuroendocrine lung tumors]], [[Small cell lung cancer|small cell carcinoma of the lung]],  
** [[Adenocarcinoma of the lung pathophysiology|Atypical adenomatous hyperplasia (AAH)]] is the only sequence of morphologic change identified leading to the development of [[Adenocarcinoma of the lung|invasive adenocarcinoma of the lung.]]
** [[Adenocarcinoma of the lung pathophysiology|Atypical adenomatous hyperplasia (AAH)]] is the only sequence of [[Morphology (biology)|morphologic]] change identified leading to the development of [[Adenocarcinoma of the lung|invasive adenocarcinoma of the lung.]]
* [[Pathogenesis]] of lung cancer is thought to be result of both due to stepwise, sequence-specific and multistage [[Molecular pathology|molecular pathogenesis]] and due to accumulation and combination of [[Genetics|genetic]] and [[Epigenetics|epigenetic]] abnormalities.
* [[Pathogenesis]] of lung cancer is thought to be result of both due to stepwise, sequence-specific and multistage [[Molecular pathology|molecular pathogenesis]] and due to accumulation and combination of [[Genetics|genetic]] and [[Epigenetics|epigenetic]] abnormalities.



Revision as of 14:07, 27 February 2019

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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] Michael Maddaleni, B.S.

Overview

The pathophysiology of lung cancer includes both genetic and environmental factors. Causality of majority of lung cancer is linked to tobacco usage. Carcinogenic effects of tobacco smoking may result in DNA mis-replication and mutation. Smoking starts a cascade of events that leads to cancer development, even decades after smoking cessation. Besides smokers, patients with the history of prior respiratory tract or gastrointestinal tract cancer comprise a high-risk population. Other environmental factors include 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][2][3]

Lung cancer pathogenesis

Field of injury and field cancerization

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.[16]

Smoking

Radon gas

The association of radon gas exposure to lung cancer is described below:[27][28]

  • 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.[29]
  • 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

References

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  2. Kadara, H.; Scheet, P.; Wistuba, I. I.; Spira, A. E. (2016). "Early Events in the Molecular Pathogenesis of Lung Cancer". Cancer Prevention Research. 9 (7): 518–527. doi:10.1158/1940-6207.CAPR-15-0400. ISSN 1940-6207.
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  4. Wistuba II, Gazdar AF (2006). "Lung cancer preneoplasia". Annu Rev Pathol. 1: 331–48. doi:10.1146/annurev.pathol.1.110304.100103. PMID 18039118.
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  23. Hanspeter Witschi ITEH and Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616
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  35. 35.0 35.1 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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