||5R01CA095023-06 Interpret this number
||University Of Pittsburgh At Pittsburgh
||Inflammation and Ovarian Cancer
DESCRIPTION (provided by applicant): 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.