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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).

Record type: Article

Abstract

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.

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Published date: 8 March 2011

Identifiers

Local EPrints ID: 180377
URI: http://eprints.soton.ac.uk/id/eprint/180377
ISSN: 1078-0432
PURE UUID: 77ad0367-f7d1-4b00-8abb-a00db92c45ed

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Date deposited: 08 Apr 2011 12:59
Last modified: 18 Jul 2017 12:01

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Contributors

Author: P.D.P. Pharoah
Author: R.T. Palmieri
Author: S.J. Ramus
Author: S.A. Gayther
Author: I.L. Andrulis
Author: H.A. Anton-Culver
Author: N. Antonenkova
Author: A.C. Antoniou
Author: M.S. Beattie
Author: M. Beckmann
Author: M.J. Birrer
Author: N. Bogdanova
Author: K.L. Bolton
Author: W. Brewster
Author: A. Brooks-Wilson
Author: R. Brown
Author: R. Butzow
Author: T. Caldes
Author: M.A. Caligo
Author: I.G. Campbell
Author: J. Chang-Claude
Author: A. Chen
Author: G. Chenevix-Trench
Author: L.S. Cook
Author: F.J. Couch
Author: D.W. Cramer
Author: J.M. Cunningham
Author: E. Despierre
Author: J.A. Doherty
Author: T. Dork
Author: M. Durst
Author: Diana Eccles
Author: A.B. Ekici
Author: P.A. Fasching
Author: A. de Fazio
Author: D.A. Fenstermacher
Author: J.M. Flanagan
Author: B.L. Fridley
Author: E. Friedman
Author: B. Gao
Author: A. Gentry-Maharaj
Author: A.K. Godwin
Author: E. Goode
Author: M.T. Goodman
Author: J. Gross
Author: T.V.O. Hansen
Author: P.R. Harnett
Author: T. Heikkinen
Author: R. Hein
Author: C K. Hogdall
Author: E.V. Hogdall
Author: E. Iversen
Author: A. Jakubowska
Author: S.E. Johnatty
Author: B.Y. Karlan
Author: N.D. Kauff
Author: S.B. Kaye
Author: L.E. Kelemen
Author: L.A. Kiemeney
Author: S.K. Kjaer
Author: D. Lambrechts
Author: J.P. LaPolla
Author: C. Lazaro
Author: N.D. Le
Author: A. Leminen
Author: K. Leunen
Author: D.A. Levine
Author: Y. Lu
Author: L. Lundvall
Author: S. Macgregor
Author: T. Marees
Author: L. Massuger
Author: J.R. McLaughlin
Author: U. Menon
Author: M. Montagna
Author: K.B. Moysich
Author: S. Narod
Author: K.L. Nathanson
Author: L. Nedergaard
Author: R.B. Ness
Author: H.A. Nevanlinna
Author: S. Nickels
Author: A. Osorio
Author: J. Paul
Author: C.L. Pearce
Author: C.M. Phelan
Author: M.C. Pike
Author: P. Radice
Author: M.A. Rossing
Author: J. Schildkraut
Author: T.A. Sellers
Author: C.F. Singer
Author: H. Song
Author: D.O. Stram
Author: R. Sutphen
Author: K.L. Terry
Author: Y-Y. Tsai
Author: A.M. van Altena
Author: I. Vergote
Author: R.A. Vierkant
Author: A.F. Vitonis
Author: C. Walsh
Author: S. Wang-Gohrke
Author: B. Wappenschmidt
Author: A.H. Wu
Author: A. Ziogas
Author: A. Berchuck
Author: H.A. Risch

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