A common coding variant in CASP8 is associated with breast cancer risk by Cox Angela, Dunning Alison M, Garcia-Closas Montserrat, Balasubramanian Sabapathy, Reed Malcolm W R, Pooley Karen A, Scollen Serena, Baynes Caroline, Ponder Bruce A J, Chanock Stephen, Lissowska Jolanta, Brinton Louise, Peplonska Beata, Southey Melissa C, Hopper John L, McCredie Margaret R E, Giles Graham G, Fletcher Olivia, Johnson Nichola, dos Santos Silva Isabel, Gibson Lorna, Bojesen Stig E, Nordestgaard Børge G, Axelsson Christen K, Torres Diana, Hamann Ute, Justenhoven Christina, Brauch Hiltrud, Chang-Claude Jenny, Kropp Silke, Risch Angela, Wang-Gohrke Shan, Schürmann Peter, Bogdanova Natalia, Dörk Thilo, Fagerholm Rainer, Aaltonen Kirsimari, Blomqvist Carl, Nevanlinna Heli, Seal Sheila, Renwick Anthony, Stratton Michael R, Rahman Nazneen, Sangrajrang Suleeporn, Hughes David, Odefrey Fabrice, Brennan Paul, Spurdle Amanda B, Chenevix-Trench Georgia, Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer, Beesley Jonathan, Mannermaa Arto, Hartikainen Jaana, Kataja Vesa, Kosma Veli-Matti, Couch Fergus J, Olson Janet E, Goode Ellen L, Broeks Annegien, Schmidt Marjanka K, Hogervorst Frans B L, Van't Veer Laura J, Kang Daehee, Yoo Keun-Young, Noh Dong-Young, Ahn Sei-Hyun, Wedrén Sara, Hall Per, Low Yen-Ling, Liu Jianjun, Milne Roger L, Ribas Gloria, Gonzalez-Neira Anna, Benitez Javier, Sigurdson Alice J, Stredrick Denise L, Alexander Bruce H, Struewing Jeffery P, Pharoah Paul D P, Easton Douglas F, Breast Cancer Association Consortium in Nature genetics (2007).

[PMID: 17293864] PubMed


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; P(trend) = 1.1 x 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; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.

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