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Title: Consortium analysis of 7 candidate SNPs for ovarian cancer.
Authors: Ramus SJ,  Vierkant RA,  Johnatty SE,  Pike MC,  Van Den Berg DJ,  Wu AH,  Pearce CL,  Menon U,  Gentry-Maharaj A,  Gayther SA,  Dicioccio RA,  McGuire V,  Whittemore AS,  Song H,  Easton DF,  Pharoah PD,  Garcia-Closas M,  Chanock S,  Lissowska J,  Brinton L,  Terry KL,  Cramer DW,  Tworoger SS,  Hankinson SE,  Berchuck A,  Moorman PG,  Schildkraut JM,  Cunningham JM,  Liebow M,  Kjaer SK,  Hogdall E,  Hogdall C,  Blaakaer J,  Ness RB,  Moysich KB,  Edwards RP,  Carney ME,  Lurie G,  Goodman MT,  Wang-Gohrke S,  Kropp S,  Chang-Claude J,  Australian Ovarian Cancer Study Group,  Australian Cancer Study (Ovarian Cancer),  Webb PM,  Chen X,  Beesley J,  Chenevix-Trench G,  Goode EL,  Ovarian Cancer Association Consortium
Journal: Int J Cancer
Date: 2008 Jul 15
Branches: HREB, LTG, CGR
PubMed ID: 18431743
PMC ID: PMC2667795
Abstract: 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.