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Consortium analysis of 7 candidate SNPs for ovarian cancer
Author(s) -
Ramus Susan J.,
Vierkant Robert A.,
Johnatty Sharon E.,
Pike Malcolm C.,
Van Den Berg David J.,
Wu Anna H.,
Pearce Celeste Leigh,
Me Usha,
GentryMaharaj Aleksandra,
Gayther Simon A.,
DiCioccio Richard A.,
McGuire Valerie,
Whittemore Alice S.,
Song Honglin,
Easton Douglas F.,
Pharoah Paul D.P.,
GarciaClosas Montserrat,
Chanock Stephen,
Lissowska Jolanta,
Brinton Louise,
Terry Kathryn L.,
Cramer Daniel W.,
Tworoger Shelley S.,
Hankinson Susan E.,
Berchuck Andrew,
Moorman Patricia G.,
Schildkraut Joellen M.,
Cunningham Julie M.,
Liebow Mark,
Kjaer Susanne Krüger,
Hogdall Estrid,
Hogdall Claus,
Blaakaer Jan,
Ness Roberta B.,
Moysich Kirsten B.,
Edwards Robert P.,
Carney Michael E.,
Lurie Galina,
Goodman Marc T.,
WangGohrke Shan,
Kropp Silke,
ChangClaude Jenny,
Webb Penelope M.,
Chen Xiaoqing,
Beesley Jonathan,
ChenevixTrench Georgia,
Goode Ellen L.
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23448
Subject(s) - single nucleotide polymorphism , ovarian cancer , odds ratio , oncology , medicine , breast cancer , confidence interval , genotype , case control study , cancer , snp , cdkn2a , biology , genetics , gene
The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA , N372H (rs144848) in BRCA2 , rs2854344 in intron 17 of RB1 , rs2811712 5′ flanking CDKN2A , rs523349 in the 3′ UTR of SRD5A2 , D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1 . Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non‐Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79–1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76–0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79–1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA , when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01–1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01–1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach. © 2008 Wiley‐Liss, Inc.