Abstract CN07-03: Polymorphisms in miRNA binding sites as risk factors for cancer development

Abstract

Abstract Purpose: Ovarian cancer is the single most deadly form of cancer specific to women, largely due to a lack of known risk factors or genetic markers. The KRAS oncogene and altered levels of the microRNA let-7 are associated with increased risk of developing solid tumors, such as ovarian cancer. We investigated a single nucleotide variant (rs61764370) that disrupts a let-7 microRNA binding site in the KRAS oncogene as a biomarker of ovarian cancer risk. Methods: Specimens were obtained from non-selected ovarian cancer patients in three independent cohorts (n = 445) and two independent ovarian case-control studies. Specimens from ovarian cancer patients with hereditary breast and ovarian cancer (HBOC) syndrome (n = 52) and their family members were also collected. Results: rs61764370 is in greater than 30% of non-selected ovarian cancer cases and is a marker for a significant increased risk of developing ovarian cancer by case control analysis (n = 201, OR = 2.46, CI = 1.14–5.29, p = .020). This was validated in a second independent ovarian case-control (n = 648). Furthermore, rs61764370 was identified in 58% of HBOC patients without BRCA1 or BRCA2 mutations (n = 24, p < 0.001), therefore previously considered uninformative, as well as in their family members with cancer. Conclusions: These findings support the hypothesis that rs61764370 is a genetic marker of increased risk of developing ovarian cancer, and suggests that rs61764370 may be a new biomarker of risk for HBOC families without other known genetic abnormalities. Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN07-03.