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

Angela Cox, Alison M. Dunning, Montserrat Garcia-Closas, Sabapathy Balasubramanian, Malcolm W.R. Reed, Karen A. Pooley, Serena Scollen, Caroline Baynes, Bruce A.J. Ponder, Stephen Chanock, Jolanta Lissowska, Louise Brinton, Beata Peplonska, Melissa C. Southey, John L. Hopper, Margaret R.E. McCredie, Graham G. Giles, Olivia Fletcher, Nichola Johnson, Isabel Dos Santos SilvaLorna Gibson, Stig E. Bojesen, Børge G. Nordestgaard, Christen K. Axelsson, Diana Torres, Ute Hamann, Christina Justenhoven, Hiltrud Brauch, Jenny Chang-Claude, Silke Kropp, Angela Risch, Shan Wang-Gohrke, Peter Schürmann, Natalia Bogdanova, Thilo Dörk, Rainer Fagerholm, Kirsimari Aaltonen, Carl Blomqvist, Heli Nevanlinna, Sheila Seal, Anthony Renwick, Michael R. Stratton, Nazneen Rahman, Suleeporn Sangrajrang, David Hughes, Fabrice Odefrey, Paul Brennan, Amanda B. Spurdle, Georgia Chenevix-Trench, Jonathan Beesley, Arto Mannermaa, Jaana Hartikainen, Vesa Kataja, Veli Matti Kosma, Fergus J. Couch, Janet E. Olson, Ellen L. Goode, Annegien Broeks, Marjanka K. Schmidt, Frans B.L. Hogervorst, Laura J.Van t. Veer, Daehee Kang, Keun Young Yoo, Dong Young Noh, Sei Hyun Ahn, Sara Wedrén, Per Hall, Yen Ling Low, Jianjun Liu, Roger L. Milne, Gloria Ribas, Anna Gonzalez-Neira, Javier Benitez, Alice J. Sigurdson, Denise L. Stredrick, Bruce H. Alexander, Jeffery P. Struewing, Paul D.P. Pharoah, Douglas F. Easton

Research output: Contribution to journalArticlepeer-review

425 Scopus citations


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 × 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.

Original languageEnglish (US)
Pages (from-to)352-358
Number of pages7
JournalNature Genetics
Issue number3
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Genetics


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