A common coding variant in CASP8 is associated with breast cancer risk.
;
Lorna 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;
Kathleen Cunningham Foundation Consortium for Research into Fami;
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 BL 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 DP Pharoah;
Douglas F Easton;
Breast Cancer Association Consortium;
(2007)
A common coding variant in CASP8 is associated with breast cancer risk.
Nature genetics, 39 (3).
pp. 352-358.
ISSN 1061-4036
DOI: 10.1038/ng1981
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.