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Correspondence |

COPD and Lung Cancer Linked at a Molecular Genetic LevelCOPD and Lung Cancer FREE TO VIEW

Robert P. Young, MD, PhD; Raewyn J. Hopkins, RN, MPH
Author and Funding Information

From the Schools of Biological Sciences and Health Sciences, University of Auckland.

Correspondence to: Robert P. Young, MD, PhD, Respiratory Genetics Group, PO Box 26161, 1344 Epsom, Auckland, New Zealand; e-mail: roberty@adhb.govt.nz


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;140(1):266-267. doi:10.1378/chest.11-0220
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To the Editor:

We read with interest the recent editorial by Strange (December 2010),1 who suggests that with a greater understanding of COPD may come a greater understanding of lung cancer biology. Here, we review evidence from recently published genetic epidemiologic studies that supports this view by showing COPD and lung cancer are linked at a molecular genetic level.

In 2009, we showed that COPD affects between 50% and 80% of those diagnosed with lung cancer (depending on diagnostic criteria), more than sixfold that seen in smokers with comparable smoking histories randomly recruited from the community.2 Recent advances in genetic epidemiology have identified genetic loci implicating three genes in the development of COPD: the nicotinic acetylcholine receptor gene (α35 subunits) on chromosome 15q25 (CHRNA3/5) (susceptibility effect), the hedgehog interacting protein on chromosome 4q31 (HHIP) (protective effect), and the family with sequence familiarity 13 member A gene on chromosome 4q22 (FAM13A) (protective effect). Although these genes were first identified through genome-wide association studies involving thousands of subjects, their dual role in COPD and lung cancer was established in a case-control study wherein these genetic associations were examined in smokers with normal lung function, those with COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] 2+ criteria) and those with histology-confirmed primary lung cancer (subgrouped by COPD subphenotype).3-5 Using this approach, we found the CHRNA gene, originally associated with an increased risk of lung cancer, was also associated with an increased risk of COPD,3 and the HHIP and FAM13A genes originally associated with reduced risk of COPD were independently associated with a reduced risk of lung cancer.4,5 These findings provide compelling evidence that COPD and lung cancer are directly linked at a molecular genetic level.

Importantly, CHRNA3/5 subunits are expressed throughout the bronchial epithelium, are activated by nicotine, and appear to modulate pulmonary inflammation.3 Similarly, HHIP is expressed on bronchial epithelium and modulates epithelial repair, smoke-induced epithelial-mesenchymal transition (premalignant transformation), and cigarette smoke-induced oncogenic transformation of bronchial epithelial cells.4 Although little is known of FAM13A function, it is also expressed on the bronchial epithelium and sequence analysis indicates FAM13A has Rho GTPase activating protein activity, suggesting both antiinflammatory and tumor suppressor function.5 Although these genetic associations and their biologic effects require confirmation in further studies, these findings provide the first evidence that COPD and lung cancer share pathogenetic mechanisms that are mediated by bronchial epithelial (airway) responses to cigarette smoke exposure.

Strange C. COPD and lung cancer: are they both airways diseases? Chest. 2010;1386:1289-1290. [CrossRef] [PubMed]
 
Young RP, Hopkins RJ, Christmas T, Black PN, Metcalf P, Gamble GD. COPD prevalence is increased in lung cancer, independent of age, sex and smoking history. Eur Respir J. 2009;342:380-386. [CrossRef] [PubMed]
 
Young RP, Hopkins RJ, Hay BA, Epton MJ, Black PN, Gamble GD. Lung cancer gene associated with COPD: triple whammy or possible confounding effect? Eur Respir J. 2008;325:1158-1164. [CrossRef] [PubMed]
 
Young RP, Whittington CF, Hopkins RJ, et al. Chromosome 4q31 locus in COPD is also associated with lung cancer. Eur Respir J. 2010;366:1375-1382. [CrossRef] [PubMed]
 
Young RP, Hopkins RJ, Hay BA, et al. FAM13Alocus in COPD independently associated with lung cancer–evidence of a molecular genetic link between COPD and lung cancer. Appl Clin Genet.20114:1-10
 

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References

Strange C. COPD and lung cancer: are they both airways diseases? Chest. 2010;1386:1289-1290. [CrossRef] [PubMed]
 
Young RP, Hopkins RJ, Christmas T, Black PN, Metcalf P, Gamble GD. COPD prevalence is increased in lung cancer, independent of age, sex and smoking history. Eur Respir J. 2009;342:380-386. [CrossRef] [PubMed]
 
Young RP, Hopkins RJ, Hay BA, Epton MJ, Black PN, Gamble GD. Lung cancer gene associated with COPD: triple whammy or possible confounding effect? Eur Respir J. 2008;325:1158-1164. [CrossRef] [PubMed]
 
Young RP, Whittington CF, Hopkins RJ, et al. Chromosome 4q31 locus in COPD is also associated with lung cancer. Eur Respir J. 2010;366:1375-1382. [CrossRef] [PubMed]
 
Young RP, Hopkins RJ, Hay BA, et al. FAM13Alocus in COPD independently associated with lung cancer–evidence of a molecular genetic link between COPD and lung cancer. Appl Clin Genet.20114:1-10
 
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