Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

Abstract

BACKGROUND The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population. METHODS To evaluate whether the CASP8 D302H (CASP10 V410I) polymorphisms modify breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers, we analyzed 7,353 (7,227) subjects of white European origin provided by 19 (18) study groups that participate in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A weighted cohort approach was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS The minor allele of CASP8 D302H was significantly associated with a reduced risk of breast cancer (per-allele HR, 0.85; 95% CI, 0.76-0.97; P(trend) = 0.011) and ovarian cancer (per-allele HR, 0.69; 95% CI, 0.53-0.89; P(trend) = 0.004) for BRCA1 but not for BRCA2 mutation carriers. The CASP10 V410I polymorphism was not associated with breast or ovarian cancer risk for BRCA1 or BRCA2 mutation carriers. CONCLUSIONS CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers but not for BRCA2 mutation carriers. IMPACT The combined application of these and other recently identified genetic risk modifiers could in the future allow better individual risk calculation and could aid in the individualized counseling and decision making with respect to preventive options in BRCA1 mutation carriers.

DOI: 10.1158/1055-9965.EPI-10-0517

4 Figures and Tables

Cite this paper

@article{Engel2010AssociationOT, title={Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.}, author={Christoph Engel and Beatrix Versmold and Barbara Wappenschmidt and Jacques Simard and Douglas F. Easton and Susan Peock and Margaret R Cook and Clare T. Oliver and Debra Frost and Rebecca Mayes and D Gareth R Evans and Rosalind Eeles and Joan Paterson and Carole Brewer and Lesley McGuffog and Antonis C. Antoniou and Dominique Stoppa-Lyonnet and Olga Sinilnikova and Laure Barjhoux and Marc Paul Frenay and C{\'e}cile Michel and Dominique Leroux and H{\'e}l{\'e}ne Dreyfus and Christine Toulas and Laurence Gladieff and Nancy A Uhrhammer and Yves-Jean Jean Bignon and Alfons Meindl and Norbert Arnold and Raymonda Varon-Mateeva and D Niederacher and Sabine Preisler-Adams and Karin Kast and Helmut Deissler and Christian Sutter and Dorothea Gadzicki and Georgia Chenevix-Trench and Amanda B. Spurdle and Xiaoqing Chen and Jonathan Beesley and H{\aa}kan Olsson and Ulf Kristoffersson and H Ehrencrona and Annelie Liljegren and Rob B van der Luijt and Theo A. M. van Os and Flora E van Leeuwen and Susan Domchek and Timothy R. Rebbeck and Katherine Nathanson and A Osorio and Teresa Ram{\'o}n Y Cajal and Irene Konstantopoulou and Javier J Benitez and Eitan Friedman and Bella Kaufman and Yael Laitman and Phuong L. Mai and Mark H Greene and Heli Nevanlinna and Kristiina Aittom{\"a}ki and Csilla Szabo and Trinidad Cald{\'e}s and Fergus J. Couch and Irene L Andrulis and Andrew K. Godwin and Ute Hamann and Rita Schmutzler}, journal={Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, year={2010}, volume={19 11}, pages={2859-68} }