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Polymorphisms in Inflammation-Related Genes and Risk of Smoking-associated Lung Cancer and Chronic Obstructive Pulmonary Disease

Du, Yan (2011) Polymorphisms in Inflammation-Related Genes and Risk of Smoking-associated Lung Cancer and Chronic Obstructive Pulmonary Disease. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Lung cancer and chronic obstructive pulmonary disease (COPD) are the leading causes of morbidity and mortality in the US. Despite the appreciation of the central role of smoking in the development of both diseases, only a relatively small number of smokers (15%-20%) develops lung cancer and/or COPD. This suggests that other factors including inherited genetic variation may play a role. Cigarette smoking induces inflammation; therefore, functionally relevant polymorphisms in inflammation-related genes may affect risk of smoking-associated lung cancer and/or COPD. The primary goals of this research were to evaluate eicosanoid pathway (IL1B, COX-2, PPARã) gene polymorphisms and cytokine (TGFB1, IL6, IL10) gene polymorphisms in relation to lung cancer risk (484 cases/866 controls); and cytokine (TGFB1, IL6, IL10) gene polymorphisms in relation to COPD (airflow obstruction and emphysema) risk (N=866). We utilized data and specimens from Project 4 of the University of Pittsburgh Cancer Institute Specialized Program of Research Excellence (SPORE) in Lung Cancer. In our study population, IL1B rs1143634 minor allele carriers had a decreased risk of lung cancer (OR=0.73, 95%CI=0.56-0.95) compared to major allele homozygote. There was a strong interaction between PPARã rs1801282 and sex (Pinteraction=0.003), female minor allele carriers were at a reduced risk of lung cancer (OR=0.58, 95%CI=0.37-0.91), while male minor allele carriers showed a non-significant increased risk (OR=1.45, 95%CI=0.96-2.19) compared to major allele homozygotes. In the analyses of COPD, TGFB1 rs2241712 was found associated with airflow obstruction severity as measured by Global Initiative for Obstructive Lung Disease (GOLD) (Cochran-Mantel-Haenszel 1degree freedom nonzero correlation P=0.02), minor allele carriers were at a decreased risk of developing the disease (any vs. no airflow obstruction, dominant model OR=0.73, 95%CI=0.55-0.98). Enhancing our knowledge of lung cancer and COPD genetics is a significant contribution to public health as it may result in the development of new prevention and treatment strategies.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Du, Yansophiedphoenix@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWeissfeld, Joel LJWEPID@pitt.eduJWEPID
Committee MemberDiergaarde, Brendadiergaardeb@upmc.eduBBD3
Committee MemberFeingold, Eleanorfeingold@pitt.eduFEINGOLD
Committee MemberSciurba, Frank Csciurbafc@upmc.eduFCS
Committee MemberRomkes, Marjorieromkes@pitt.eduROMKES
Date: 29 June 2011
Date Type: Completion
Defense Date: 29 March 2011
Approval Date: 29 June 2011
Submission Date: 5 April 2011
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: DrPH - Doctor of Public Health
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Lung Cancer; Inflammation; COPD; Polymorphisms
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04052011-134026/, etd-04052011-134026
Date Deposited: 10 Nov 2011 19:34
Last Modified: 19 Dec 2016 14:35
URI: http://d-scholarship.pitt.edu/id/eprint/6789

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