The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing

Paul D P Pharoah, Rachel T Palmieri, Susan J Ramus, Simon A Gayther, Irene L Andrulis, Hoda A Anton-Culver, Natalia Antonenkova, Antonis C Antoniou, Study Group Of Bcfr Investigators, Mary S Beattie, Matthias W Beckmann, Michael J Birrer, Natalia Bogdanova, Kelly L Bolton, Wendy Brewster, Angela Brooks-Wilson, Robert Brown, Ralf Bützow, Trinidad Caldes, Maria A CaligoIan G Campbell, Jenny Chang-Claude, Y Ann Chen, Georgia Chenevix-Trench, Linda S Cook, Fergus J Couch, Daniel W Cramer, Julie M Cunningham, Evelyn Despierre, Jennifer A Doherty, Thilo Dork, Matthias Durst, Diana Eccles, Arif B Ekici, Study Group Of Embrace Investigators, Peter A Fasching, Anna de Fazio, David Fenstermacher, James M Flanagan, Brooke L Fridley, Eitan Friedman, Bo Gao, Study Group Of Gemo Study Collaborators, Aleksandra Gentry-Maharaj, Andrew K Godwin, Ellen L Goode, Marc T Goodman, Jenny Gross, Thomas van Overeem Hansen, Paul R Harnett, Study Group Of Hebon Investigators, Tuomas Heikkinen, Rebecca Hein, Claus K Hogdall, Estrid Vilma Solyom Høgdall, Edwin Iversen, Anna Jakubowska, Sharon E Johnatty, Beth Y Karlan, Noah D Kauff, Stanley B Kaye, Study Group Of Kconfab Investigators, Linda E Kelemen, Lambertus A Kiemeney, Susanne K Kjaer, Diether Lambrechts, James P Lapolla, Conxi Lazaro, Nhu D Le, Arto Leminen, Karin Leunen, Douglas A Levine, Yi Lu, Lene Lundvall, Stuart Macgregor, Tamara Marees, Leon Massuger, John McLaughlin, Usha Menon, Marco Montagna, Kirsten B Moysich, Steven A Narod, Katherine L Nathanson, Lotte Nedergaard, Roberta B Ness, Heli A Nevanlinna, Stefan Nickels, Ana Osorio, James Paul, Celeste Leigh Pearce, Catherine M Phelan, Malcolm C Pike, Paolo Radice, Maria Rossing, Joellen M Schildkraut, Thomas A Sellers, Christian F Singer, Honglin Song, Daniel O Stram, Rebecca Sutphen, Study Group Of Swe-Brca Investigators, Kathryn L Terry, Ya-Yu Tsai, Anne M van Altena, Ignace Vergote, Robert A Vierkant, Allison F Vitonis, Christine Walsh, Shan Wang-Gohrke, Barbara Wappenschmidt, Anna H Wu, Argyrios Ziogas, Andrew Berchuck, Harvey Risch

44 Citationer (Scopus)


PURPOSE: An assay for the single nucleotide polymorphism (SNP) rs61764370 has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'UTR miRNA binding site of the KRAS oncogene, and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published paper, analyzing fewer than 1,000 subjects in total, has examined this association. EXPERIMENTAL DESIGN: Risk association was evaluated in 8,669 cases of invasive EOC and 10,012 controls from nineteen studies participating in the Ovarian Cancer Association Consortium, and in 683 cases and 2,044 controls carrying BRCA1 mutations from studies in the Consortium of Investigators of Modifiers of BRCA1/2. Prognosis association was also examined in a subset of five studies with progression-free survival data and eighteen studies with all-cause mortality data.RESULTS: No evidence of association was observed between genotype and risk of unselected EOC (odds ratio (OR)=1.02, 95% confidence interval (CI)=0.95-1.10), serous EOC (OR=1.08, 95%CI=0.98-1.18), familial EOC (OR=1.09, 95%CI=0.78-1.54), or among women carrying deleterious mutations in BRCA1 (OR=1.09, 95%CI=0.88-1.36). There was little evidence for association with survival time among unselected cases (hazard ratio (HR)=1.10, 95%CI=0.99-1.22), among serous cases (HR=1.12, 95%CI=0.99-1.28), or with progression-free survival in 540 cases treated with carboplatin and paclitaxel (HR=1.18, 95%CI=0.93-1.52).CONCLUSIONS: These data exclude the possibility of an association between rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer. Use of this SNP for ovarian cancer clinical risk prediction therefore appears unwarranted.
TidsskriftClinical Cancer Research
Udgave nummer11
Sider (fra-til)3742-50
Antal sider9
StatusUdgivet - 13 apr. 2011


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