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Association of the Variants CASP8 D302H and CASP10 V410I with Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

Engel, Christoph; Versmold, Beatrix; Wappenschmidt, Barbara; Simard, Jacques; Easton, Douglas F; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra and Mayes, Rebecca, et al. (2010) In Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 19. p.2859-2868
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... (More)
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. Cancer Epidemiol Biomarkers Prev; 19(11); 2859-68. ©2010 AACR. (Less)
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Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
volume
19
pages
2859 - 2868
publisher
American Association for Cancer Research
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  • wos:000283991600020
  • pmid:20978178
  • scopus:78549237225
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-10-0517
language
English
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707740eb-2f8c-40dd-8d48-9edc43292ea6 (old id 1710693)
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http://www.ncbi.nlm.nih.gov/pubmed/20978178?dopt=Abstract
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2010-11-05 14:29:19
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@article{707740eb-2f8c-40dd-8d48-9edc43292ea6,
  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. Cancer Epidemiol Biomarkers Prev; 19(11); 2859-68. ©2010 AACR.},
  author       = {Engel, Christoph and Versmold, Beatrix and Wappenschmidt, Barbara and Simard, Jacques and Easton, Douglas F and Peock, Susan and Cook, Margaret and Oliver, Clare and Frost, Debra and Mayes, Rebecca and Evans, D Gareth and Eeles, Rosalind and Paterson, Joan and Brewer, Carole and McGuffog, Lesley and Antoniou, Antonis C and Stoppa-Lyonnet, Dominique and Sinilnikova, Olga M and Barjhoux, Laure and Frenay, Marc and Michel, Cécile and Leroux, Dominique and Dreyfus, Helene and Toulas, Christine and Gladieff, Laurence and Uhrhammer, Nancy and Bignon, Yves-Jean and Meindl, Alfons and Arnold, Norbert and Varon-Mateeva, Raymonda and Niederacher, Dieter and Preisler-Adams, Sabine and Kast, Karin and Deissler, Helmut and Sutter, Christian and Gadzicki, Dorothea and Chenevix-Trench, Georgia and Spurdle, Amanda B and Chen, Xiaoqing and Beesley, Jonathan and Olsson, Håkan and Kristoffersson, Ulf and Ehrencrona, Hans and Liljegren, Annelie and van der Luijt, Rob B and van Os, Theo A and van Leeuwen, Flora E and Domchek, Susan M and Rebbeck, Timothy R and Nathanson, Katherine L and Osorio, Ana and Ramón Y Cajal, Teresa and Konstantopoulou, Irene and Benítez, Javier and Friedman, Eitan and Kaufman, Bella and Laitman, Yael and Mai, Phuong L and Greene, Mark H and Nevanlinna, Heli and Aittomäki, Kristiina and Szabo, Csilla I and Caldes, Trinidad and Couch, Fergus J and Andrulis, Irene L and Godwin, Andrew K and Hamann, Ute and Schmutzler, Rita K},
  issn         = {1538-7755},
  language     = {eng},
  pages        = {2859--2868},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
  title        = {Association of the Variants CASP8 D302H and CASP10 V410I with Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-10-0517},
  volume       = {19},
  year         = {2010},
}