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(Unpublished)
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Unpublished |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: |
|
| ETD Committee: |
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| 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: |
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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