Abstract 1856: A KRAS-variant as a putative biomarker of ovarian cancer risk

Abstract

Abstract Purpose: Ovarian cancer is the single most deadly form of women's cancer, 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 an increased risk of developing solid tumors. We investigated the association of a single nucleotide variant (rs61764370), referred to as the KRAS-variant, that disrupts a let-7 microRNA binding site in the KRAS oncogene 1, and ovarian cancer risk. Methods: Specimens were obtained from non-selected ovarian cancer patients in three independent cohorts (n = 457) and two independent ovarian case-control studies. Specimens from ovarian cancer patients with hereditary breast and ovarian cancer (HBOC) syndrome (n = 58) and their family members were also collected. Findings: The KRAS-variant is found in greater than 29% of non-selected ovarian cancer cases and is a marker for a significant increased risk of developing ovarian cancer by case control analysis (OR = 2.46, CI = 1.14-5.29, p = .020, n = 201). This was validated in a second independent ovarian case-control (n = 630). The KRAS-variant was also identified in 60% of HBOC patients without BRCA1 or BRCA2 mutations (n = 25, p < 0.001), previously considered uninformative, as well as in their family members with cancer. Interpretation: These findings support the hypothesis that the KRAS-variant is a genetic marker of an increased risk of developing ovarian cancer, and suggests that the KRAS-variant may be a new biomarker of risk for HBOC families without other known genetic abnormalities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1856.