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

Pharoah, P.D.P., Palmieri, R.T., Ramus, S.J., Gayther, S.A., Andrulis, I.L., Anton-Culver, H.A., Antonenkova, N., Antoniou, A.C., Beattie, M.S., Beckmann, M., Birrer, M.J., Bogdanova, N., Bolton, K.L., Brewster, W., Brooks-Wilson, A., Brown, R., Butzow, R., Caldes, T., Caligo, M.A., Campbell, I.G., Chang-Claude, J., Chen, A., Chenevix-Trench, G., Cook, L.S., Couch, F.J., Cramer, D.W., Cunningham, J.M., Despierre, E., Doherty, J.A., Dork, T., Durst, M., Eccles, Diana, Ekici, A.B., Fasching, P.A., de Fazio, A., Fenstermacher, D.A., Flanagan, J.M., Fridley, B.L., Friedman, E., Gao, B., Gentry-Maharaj, A., Godwin, A.K., Goode, E., Goodman, M.T., Gross, J., Hansen, T.V.O., Harnett, P.R., Heikkinen, T., Hein, R., Hogdall, C K., Hogdall, E.V., Iversen, E., Jakubowska, A., Johnatty, S.E., Karlan, B.Y., Kauff, N.D., Kaye, S.B., Kelemen, L.E., Kiemeney, L.A., Kjaer, S.K., Lambrechts, D., LaPolla, J.P., Lazaro, C., Le, N.D., Leminen, A., Leunen, K., Levine, D.A., Lu, Y., Lundvall, L., Macgregor, S., Marees, T., Massuger, L., McLaughlin, J.R., Menon, U., Montagna, M., Moysich, K.B., Narod, S., Nathanson, K.L., Nedergaard, L., Ness, R.B., Nevanlinna, H.A., Nickels, S., Osorio, A., Paul, J., Pearce, C.L., Phelan, C.M., Pike, M.C., Radice, P., Rossing, M.A., Schildkraut, J., Sellers, T.A., Singer, C.F., Song, H., Stram, D.O., Sutphen, R., Terry, K.L., Tsai, Y-Y., van Altena, A.M., Vergote, I., Vierkant, R.A., Vitonis, A.F., Walsh, C., Wang-Gohrke, S., Wappenschmidt, B., Wu, A.H., Ziogas, A., Berchuck, A. and Risch, H.A. Study Group of BCFR Investigators (2011) The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing Clinical Cancer Research (doi:10.1158/1078-0432.CCR-10-3405). (PMID:21385923).


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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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1158/1078-0432.CCR-10-3405
ISSNs: 1078-0432 (print)
ePrint ID: 180377
Date :
Date Event
8 March 2011Published
Date Deposited: 08 Apr 2011 12:59
Last Modified: 18 Apr 2017 02:31
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