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Ratner E , Lu LG , Boeke M , Barnett R , Nallur S , Chin LJ , Pelletier C , Blitzblau R , Tassi R , Paranjape T , Hui P , Godwin AK , Yu H , Risch H , Rutherford T , Schwartz P , Santin A , Matloff E , Zelterman D , Slack FJ , Weidhaas JB
A KRAS-Variant in Ovarian Cancer Acts as a Genetic Marker of Cancer Risk
Cancer Research. 2010 Aug;70(16) :6509-6515
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Ovarian cancer (OC) is the single most deadly form of women's cancer, typically presenting as an advanced disease at diagnosis in part due to a lack of known risk factors or genetic markers of risk. The KRAS oncogene and altered levels of the microRNA (miRNA) let-7 are associated with an increased risk of developing solid tumors. In this study, we investigated a hypothesized association between an increased risk of OC and a variant allele of KRAS at rs61764370, referred to as the KRAS-variant, which disrupts a let-7 miRNA binding site in this oncogene. Specimens obtained were tested for the presence of the KRAS-variant from nonselected OC patients in three independent cohorts, two independent ovarian case-control studies, and OC patients with hereditary breast and ovarian cancer syndrome (HBOC) as well as their family members. Our results indicate that the KRAS-variant is associated with more than 25% of nonselected OC cases. Further, we found that it is a marker for a significant increased risk of developing OC, as confirmed by two independent case-control analyses. Lastly, we determined that the KRAS-variant was present in 61% of HBOC patients without BRCA1 or BRCA2 mutations, previously considered uninformative, as well as in their family members with cancer. Our findings strongly support the hypothesis that the KRAS-variant is a genetic marker for increased risk of developing OC, and they suggest that the KRAS-variant may be a new genetic marker of cancer risk for HBOC families without other known genetic abnormalities. Cancer Res; 70(16); 6509-15. (C)2010 AACR.
Ratner, Elena Lu, Lingeng Boeke, Marta Barnett, Rachel Nallur, Sunitha Chin, Lena J. Pelletier, Cory Blitzblau, Rachel Tassi, Renata Paranjape, Trupti Hui, Pei Godwin, Andrew K. Yu, Herbert Risch, Harvey Rutherford, Thomas Schwartz, Peter Santin, Alessandro Matloff, Ellen Zelterman, Daniel Slack, Frank J. Weidhaas, Joanne B. Amer assoc cancer research Philadelphia 638ik