Engel, Christoph ORCID: 0000-0002-7247-282X, Versmold, Beatrix, Wappenschmidt, Barbara, Simard, Jacques ORCID: 0000-0001-6906-3390, Easton, Douglas F., Peock, Susan, Cook, Margaret, Oliver, Clare, Frost, Debra, Mayes, Rebecca, Evans, D. Gareth, Eeles, Rosalind ORCID: 0000-0002-3698-6241, Paterson, Joan, Brewer, Carole, McGuffog, Lesley, Antoniou, Antonis C., Stoppa-Lyonnet, Dominique, Sinilnikova, Olga M., Barjhoux, Laure, Frenay, Marc, Michel, Cecile, Leroux, Dominique, Dreyfus, Helene, Toulas, Christine ORCID: 0000-0003-1261-1725, Gladieff, Laurence, Uhrhammer, Nancy, Bignon, Yves-Jean, Meindl, Alfons, Arnold, Norbert ORCID: 0000-0003-4523-8808, Varon-Mateeva, Raymonda, Niederacher, Dieter, Preisler-Adams, Sabine, Kast, Karin, Deissler, Helmut, Sutter, Christian, Gadzicki, Dorothea, Chenevix-Trench, Georgia ORCID: 0000-0002-1878-2587, Spurdle, Amanda B., Chen, Xiaoqing, Beesley, Jonathan ORCID: 0000-0003-1942-325X, Olsson, Hakan ORCID: 0000-0002-8794-9635, Kristoffersson, Ulf, Ehrencrona, Hans ORCID: 0000-0002-5589-3622, Liljegren, Annelie, van der Luijt, Rob B., van Os, Theo A., van Leeuwen, Flora E., Domchek, Susan M., Rebbeck, Timothy R., Nathanson, Katherine L., Osorio, Ana ORCID: 0000-0001-8124-3984, Ramon y Cajal, Teresa, Konstantopoulou, Irene ORCID: 0000-0002-0470-0309, Benitez, Javier, Friedman, Eitan, Kaufman, Bella, Laitman, Yael, Mai, Phuong L., Greene, Mark H., Nevanlinna, Heli ORCID: 0000-0002-0916-2976, Aittomaki, Kristiina, Szabo, Csilla I., Caldes, Trinidad, Couch, Fergus J., Andrulis, Irene L., Godwin, Andrew K., Hamann, Ute and Schmutzler, Rita K. (2010). Association of the Variants CASP8 D302H and CASP10 V410I with Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. Cancer Epidemiol. Biomarkers Prev., 19 (11). S. 2859 - 2869. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1055-9965

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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. (C)2010 AACR.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Engel, ChristophUNSPECIFIEDorcid.org/0000-0002-7247-282XUNSPECIFIED
Versmold, BeatrixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wappenschmidt, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simard, JacquesUNSPECIFIEDorcid.org/0000-0001-6906-3390UNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peock, SusanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cook, MargaretUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oliver, ClareUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frost, DebraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayes, RebeccaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evans, D. GarethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eeles, RosalindUNSPECIFIEDorcid.org/0000-0002-3698-6241UNSPECIFIED
Paterson, JoanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brewer, CaroleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGuffog, LesleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antoniou, Antonis C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoppa-Lyonnet, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sinilnikova, Olga M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barjhoux, LaureUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frenay, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michel, CecileUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leroux, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dreyfus, HeleneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toulas, ChristineUNSPECIFIEDorcid.org/0000-0003-1261-1725UNSPECIFIED
Gladieff, LaurenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uhrhammer, NancyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bignon, Yves-JeanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meindl, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnold, NorbertUNSPECIFIEDorcid.org/0000-0003-4523-8808UNSPECIFIED
Varon-Mateeva, RaymondaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niederacher, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Preisler-Adams, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kast, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deissler, HelmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sutter, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gadzicki, DorotheaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDorcid.org/0000-0002-1878-2587UNSPECIFIED
Spurdle, Amanda B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, XiaoqingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beesley, JonathanUNSPECIFIEDorcid.org/0000-0003-1942-325XUNSPECIFIED
Olsson, HakanUNSPECIFIEDorcid.org/0000-0002-8794-9635UNSPECIFIED
Kristoffersson, UlfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ehrencrona, HansUNSPECIFIEDorcid.org/0000-0002-5589-3622UNSPECIFIED
Liljegren, AnnelieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Luijt, Rob B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Os, Theo A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Leeuwen, Flora E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Domchek, Susan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rebbeck, Timothy R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nathanson, Katherine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Osorio, AnaUNSPECIFIEDorcid.org/0000-0001-8124-3984UNSPECIFIED
Ramon y Cajal, TeresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konstantopoulou, IreneUNSPECIFIEDorcid.org/0000-0002-0470-0309UNSPECIFIED
Benitez, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedman, EitanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaufman, BellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laitman, YaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mai, Phuong L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greene, Mark H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nevanlinna, HeliUNSPECIFIEDorcid.org/0000-0002-0916-2976UNSPECIFIED
Aittomaki, KristiinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szabo, Csilla I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caldes, TrinidadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Godwin, Andrew K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamann, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-493041
DOI: 10.1158/1055-9965.EPI-10-0517
Journal or Publication Title: Cancer Epidemiol. Biomarkers Prev.
Volume: 19
Number: 11
Page Range: S. 2859 - 2869
Date: 2010
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 1055-9965
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CASPASE-8 GENE; INACTIVATING MUTATIONS; COMMON VARIANTS; REDUCED RISK; CELL-CYCLE; APOPTOSIS; SUSCEPTIBILITY; POLYMORPHISMS; PREDISPOSITION; CARCINOMASMultiple languages
Oncology; Public, Environmental & Occupational HealthMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/49304

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