Type II diabetes, related biomarkers and medications, and ovarian cancer risk

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PROJECT SUMMARY Ovarian cancer is the 5th leading cause of cancer death among women in the United States. No reliable screening method exists for the early detection of ovarian cancer thus it is critical to identify potentially modifiable ovarian cancer risk factors to inform prevention strategies. Type II diabetes is a preventable chronic disease and over the past few decades its prevalence has been rising. Type II diabetes has been associated with higher risks of some cancers, however methodologic challenges have limited previous studies examining the association between type II diabetes and ovarian cancer risk. The overall goal of this application is to prospectively examine the association between T2D, related medications and biomarkers, and ovarian cancer risk, overall and by tumor characteristics. We propose to examine these complex associations by leveraging resources from 14 studies participating in the Ovarian Cancer Cohort Consortium (OC3), specifically testing the following hypotheses/aims: Aim 1. Examine the association between T2D, including duration and age at diagnosis, and ovarian cancer risk, overall, by histotype, and by tumor marker expression. Aim 2. Interrogate the impact of type of T2D therapy (e.g., metformin, insulin), and changes in therapy, on ovarian cancer risk, overall, by histotype, and by tumor marker expression. In addition, we will examine whether metformin use in combination with low-dose daily aspirin use has a synergistic impact on ovarian cancer risk reduction. Aim 3. In an exploratory aim, examine the associations between different T2D “phenotypes” as defined by T2D related biomarkers (fasting insulin, fasting glucose, HOMA-IR, adiponectin) in a nested case-control study of ovarian cancer cases and controls. This aim will allow us to more clearly understand the mechanism(s) underlying the T2D-ovarian cancer association. The proposed study will use baseline and follow-up data from 14 prospective cohort studies that are part of the OC3. This includes over 1,000,000 women and 5,300+ ovarian cancer cases from established prospective cohort studies with 12-37 years of follow-up. We know of no other ovarian cancer consortia in the world that permits prospective evaluation with comprehensive follow-up data on type II diabetes, medication use, and relevant ovarian cancer risk factors. Importantly, clarifying the association between type II diabetes and specific histologic subtypes may provide insight into the underlying mechanisms of ovarian cancer carcinogenesis and has the potential to improve prevention strategies.