Description
There have been several environmental factors, which have been associated with an increased risk of developing epithelial ovarian cancer. It is unclear how these environmental factors might interact with genotype. This project uses resources available within the Nurses' Health Study and the New England Ovarian Cancer case-control study to evaluate numerous polymorphisms to explore potential interactions between environmental exposures and a genotype.

The primary prevention of ovarian cancer through identification of modifiable risk factors has been an elusive goal of epidemiologic studies of the disease. The role of relatively weak but modifiable risk factors in ovarian cancer might be clarified by consistent methods of analysis of large data sets that consider interactions with relevant genes or other exposures and variation by histologic type of ovarian cancer. For this proposal, researchers working with the Nurses' Health Study (NHS) cohort and a large New England based Case-Control study (NECC) will collaborate to investigate the following primary hypotheses:

1. By free radical damage generated from chronic inflammation, genital exposure to talc increases the risk for ovarian cancer and the association may be more apparent in women with the "null" variant of GSTM1, "slow" variant of NAT2, and "G" variant of MPO.
2. By protecting against prostaglandin-induced upregulation of aromatase or other mechanisms, ovarian cancer risk is reduced by acetaminophen, ibuprofen, aspirin, or other anti-inflammatory drugs and risk may be modified by genes in CYP2C9, UGT1A6, or aromatase pathways.
3. By enhancing steroid production, caffeine consumption increases ovarian cancer risk and the association may be modified by menopausal status, cholesterol consumption, hormone use, smoking, or caffeine metabolism involving CYP1A1, CYP1A2, CYP2A6, and NAT2.
4. By scavenging reactive oxygen species or affecting growth pathways, antioxidants may reduce risk for ovarian cancer. We propose to examine possible sources of heterogeneity between our two studies for the associations between carotenoids and ovarian cancer risk as well as evaluate a new relationship between flavonoid intake and ovarian cancer risk. 
   
   
   

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