||6R03CA267113-02 Interpret this number
||Fred Hutchinson Cancer Center
||Type II Diabetes, Related Biomarkers and Medications, and Ovarian Cancer Risk
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
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.
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