The Role of KRAS rs61764370 in Invasive Epithelial Ovarian Cancer: Implications for Clinical Testing
Authors: Pharoah Paul D. P. , Palmieri Rachel T. , Ramus Susan J. , Gayther Simon A. , Andrulis Irene L. , Anton-Culver Hoda , Antonenkova Natalia , Antoniou Antonis C. , Goldgar David , Beattie Mary S. , Beckmann Matthias W. , Birrer Michael J. , Bogdanova Natalia , Bolton Kelly L. , Brewster Wendy , Brooks-Wilson Angela , Brown Robert , Butzow Ralf , Caldes Trinidad , Caligo Maria Adelaide , Campbell Ian , Chang-Claude Jenny , Chen Y. Ann , Cook Linda S. , Couch Fergus J. , Cramer Daniel W. , Cunningham Julie M. , Despierre Evelyn , Doherty Jennifer A. , Dörk Thilo , Dürst Matthias , Eccles Diana M. , Ekici Arif B. , Easton Douglas , Fasching Peter A. , de Fazio Anna , Fenstermacher David A. , Flanagan James M. , Fridley Brooke L. , Friedman Eitan , Gao Bo , Sinilnikova Olga , Gentry-Maharaj Aleksandra , Godwin Andrew K. , Goode Ellen L. , Goodman Marc T. , Gross Jenny , Hansen Thomas V. O. , Harnett Paul , Rookus Matti , Heikkinen Tuomas , Hein Rebecca , Høgdall Claus , Høgdall Estrid , Iversen Edwin S. , Jakubowska Anna , Johnatty Sharon E. , Karlan Beth Y. , Kauff Noah D. , Kaye Stanley B. , Chenevix-Trench Georgia , Kelemen Linda E. , Kiemeney Lambertus A. , Kjaer Susanne Krüger , Lambrechts Diether , LaPolla James P. , Lázaro Conxi , Le Nhu D. , Leminen Arto , Leunen Karin , Levine Douglas A. , Lu Yi , Lundvall Lene , Macgregor Stuart , Marees Tamara , Massuger Leon F. , McLaughlin John R. , Menon Usha , Montagna Marco , Moysich Kirsten B. , Narod Steven A. , Nathanson Katherine L. , Nedergaard Lotte , Ness Roberta B. , Nevanlinna Heli , Nickels Stefan , Osorio Ana , Paul Jim , Pearce Celeste Leigh , Phelan Catherine M. , Pike Malcolm C. , Radice Paolo , Rossing Mary Anne , Schildkraut Joellen M. , Sellers Thomas A. , Singer Christian F. , Song Honglin , Stram Daniel O. , Sutphen Rebecca , Lindblom Annika , Terry Kathryn L. , Tsai Ya-Yu , van Altena Anne M. , Vergote Ignace , Vierkant Robert A. , Vitonis Allison F. , Walsh Christine , Wang-Gohrke Shan , Wappenschmidt Barbara , Wu Anna H. , Ziogas Argyrios , Berchuck Andrew , Risch Harvey A. 
Published: March 2011

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 article, 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 19 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 (PFS) data and 18 studies with all-cause mortality data.

Results: No evidence of association was observed between genotype and risk of unselected EOC (OR = 1.02, 95% 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 (HR = 1.10, 95% CI: 0.99–1.22), among serous cases (HR = 1.12, 95% CI = 0.99–1.28), or with PFS 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, seems unwarranted. Clin Cancer Res; 17(11); 3742–50. ©2011 AACR.