The cause of ovarian cancer is unclear. We have suggested that inflammation may be involved. Ovulation, endometriosis, and talc use all promote inflammation, and all increase the risk of ovarian cancer; tubal ligation and hysterectomy prevent the ovaries from being exposed to inflammants, and reduce risk. Furthermore, inflammation entails DNA damage and repair, oxidative stress, and elevations in prostaglandins and cytokines, all of which may be mutagenic. Building on our track record of success with conducting ovarian cancer case-control studies, we propose a population-based study to examine the role of inflammation in the risk for ovarian cancer. We will enroll 900 women with incident ovarian cancer (cases) from hospitals in Western Pennsylvania, Northern Ohio, and Western New York. One thousand eight hundred controls, ascertained via random digit dialing, will be frequency matched to cases on age, race, and residence. Using in-person standardized interviews and blood draws, we propose to: 1) evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs) protect against ovarian cancer; 2) compare in cases and controls allelic variants in inflammatory and antinflammatory cytokines and growth factors including IL-1, TNF-a, IL-10, IGF-1 and TGF-b; 3) evaluate whether markers of past PID, i.e. higher antibody titers to chlamydia and its related heat shock protein (HSP)-60, relate to ovarian cancer; 4) in a secondary aim, explore whether allelic variants in the NSAID metabolizing enzymes CYP2C9 and UGT1A6 interact with NSAID use to reduce the risk of ovarian cancer. Exploring the relationships among inflammatory predisposition, inflammatory exposures, anti-inflammatory medications, and ovarian cancer represents a novel avenue of research. In particular, NSAID use may prove to be a potentially important chemopreventative for this often-fatal disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA095023-05
Application #
7291671
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Mikhail, Isis S
Project Start
2003-05-12
Project End
2009-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
5
Fiscal Year
2007
Total Cost
$569,950
Indirect Cost
Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Lawrenson, Kate; Iversen, Edwin S; Tyrer, Jonathan et al. (2015) Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer. Carcinogenesis 36:1341-53

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