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.
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