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.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04052011-134026 |
| Date | 29 June 2011 |
| Creators | Du, Yan |
| Contributors | Frank C. Sciurba, Marjorie Romkes, Joel L. Weissfeld, Eleanor Feingold, Brenda Diergaarde |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04052011-134026/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
Page generated in 0.0022 seconds