A common coding variant in CASP8 is associated with breast cancer risk

Cox A, Dunning AM, Garcia-Closas M, Balasubramanian S, Reed MWR, Pooley KA, Scollen S, Baynes C, Ponder BAJ, Chanock S, Lissowska J, Brinton L, Peplonska B, Southey MC, Hopper JL, E MR, McCredie MRE, Giles GG, Fletcher O, Johnson N, dos Santos Silva I, Gibson L, Bojesen SE, Nordestgaard BG, Axelsson CK, Torres D, Hamann U, Justenhoven C, Brauch H, Chang-Claude J, Kropp S, Risch A, Wang-Gohrke S, Schu¨rmann P, Bogdanova N, Do¨rk T, Fagerholm R, Aaltonen K, Blomqvist C, Nevanlinna H, Seal S, Renwick A, Stratton MR, Rahman N, Sangrajrang S, Hughes D, Odefrey F, Brennan P, Spurdle AB, Chenevix-Trench G, Beesley J, Mannermaa A, Hartikainen J, 23 V, Kataja V, 23 V-M, Kosma V-M, Couch FJ, Olson JE, Goode EL, Broeks A, Schmidt MK, Hogervorst FBL, Van’t Veer LJ, Kang D, Yoo K-Y, Noh D-Y, Ahn S-H, Wedre´n S, Hall P, Low Y-L, Liu J, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Sigurdson AJ, Stredrick DL, Alexander BH, Struewing JP, Pharoah PDP, Easton DF (2007) A common coding variant in CASP8 is associated with breast cancer risk. Nature Genetics 39:

The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9–15 studies, comprising 11,391–18,290 cases and 14,753–22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85–0.94) and 0.74 (95% c.i.: 0.62–0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; Ptrend = 1.1 10-7) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02–1.13) and 1.16 (95% c.i.: 1.08–1.25), respectively; Ptrend = 2.8 10-5). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.