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

Christoph Engel, Beatrix Versmold, Barbara Wappenschmidt, Jacques Simard, Douglas F. Easton, Susan Peock, Margaret Cook, Clare Oliver, Debra Frost, Rebecca Mayes, D. Gareth Evans, Rosalind Eeles, Joan Paterson, Carole Brewer, Lesley McGuffog, Antonis C. Antoniou, Dominique Stoppa-Lyonnet, Olga M. Sinilnikova, Laure Barjhoux, Marc FrenayCécile Michel, Dominique Leroux, Helene Dreyfus, Christine Toulas, Laurence Gladieff, Nancy Uhrhammer, Yves Jean Bignon, Alfons Meindl, Norbert Arnold, Raymonda Varon-Mateeva, Dieter Niederacher, Sabine Preisler-Adams, Karin Kast, Helmut Deissler, Christian Sutter, Dorothea Gadzicki, Georgia Chenevix-Trench, Amanda B. Spurdle, Xiaoqing Chen, Jonathan Beesley, Håkan Olsson, Ulf Kristoffersson, Hans Ehrencrona, Annelie Liljegren, Rob B. Van Der Luijt, Theo A. Van Os, Flora E. Van Leeuwen, Susan M. Domchek, Timothy R. Rebbeck, Katherine L. Nathanson, Ana Osorio, Teresa Ramón Y Cajal, Irene Konstantopoulou, Javier Benítez, Eitan Friedman, Bella Kaufman, Yael Laitman, Phuong L. Mai, Mark H. Greene, Heli Nevanlinna, Kristiina Aittomäki, Csilla I. Szabo, Trinidad Caldes, Fergus J Couch, Irene L. Andrulis, Andrew K. Godwin, Ute Hamann, Rita K. Schmutzler

Research output: Contribution to journalArticle

29 Citations (Scopus)

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; Ptrend = 0.011) and ovarian cancer (per-allele HR, 0.69; 95% CI, 0.53-0.89; Ptrend = 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 riskmodifiers 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.

Original languageEnglish (US)
Pages (from-to)2859-2868
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume19
Issue number11
DOIs
StatePublished - Nov 2010

Fingerprint

Caspase 10
Caspase 8
Ovarian Neoplasms
Breast Neoplasms
Mutation
Alleles
Confidence Intervals
Apoptosis
Case-Control Studies
Counseling
Decision Making
Research Personnel

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

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; Mayes, Rebecca; Evans, D. Gareth; Eeles, Rosalind; Paterson, Joan; Brewer, Carole; McGuffog, Lesley; Antoniou, Antonis C.; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Barjhoux, Laure; Frenay, Marc; Michel, Cécile; Leroux, Dominique; Dreyfus, Helene; Toulas, Christine; Gladieff, Laurence; Uhrhammer, Nancy; Bignon, Yves Jean; Meindl, Alfons; Arnold, Norbert; Varon-Mateeva, Raymonda; Niederacher, Dieter; Preisler-Adams, Sabine; Kast, Karin; Deissler, Helmut; Sutter, Christian; Gadzicki, Dorothea; Chenevix-Trench, Georgia; Spurdle, Amanda B.; Chen, Xiaoqing; Beesley, Jonathan; Olsson, Håkan; Kristoffersson, Ulf; Ehrencrona, Hans; 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; Ramón Y Cajal, Teresa; Konstantopoulou, Irene; Benítez, Javier; Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Mai, Phuong L.; Greene, Mark H.; Nevanlinna, Heli; Aittomäki, Kristiina; Szabo, Csilla I.; Caldes, Trinidad; Couch, Fergus J; Andrulis, Irene L.; Godwin, Andrew K.; Hamann, Ute; Schmutzler, Rita K.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 19, No. 11, 11.2010, p. 2859-2868.

Research output: Contribution to journalArticle

Engel, C, Versmold, B, Wappenschmidt, B, Simard, J, Easton, DF, Peock, S, Cook, M, Oliver, C, Frost, D, Mayes, R, Evans, DG, Eeles, R, Paterson, J, Brewer, C, McGuffog, L, Antoniou, AC, Stoppa-Lyonnet, D, Sinilnikova, OM, Barjhoux, L, Frenay, M, Michel, C, Leroux, D, Dreyfus, H, Toulas, C, Gladieff, L, Uhrhammer, N, Bignon, YJ, Meindl, A, Arnold, N, Varon-Mateeva, R, Niederacher, D, Preisler-Adams, S, Kast, K, Deissler, H, Sutter, C, Gadzicki, D, Chenevix-Trench, G, Spurdle, AB, Chen, X, Beesley, J, Olsson, H, Kristoffersson, U, Ehrencrona, H, Liljegren, A, Van Der Luijt, RB, Van Os, TA, Van Leeuwen, FE, Domchek, SM, Rebbeck, TR, Nathanson, KL, Osorio, A, Ramón Y Cajal, T, Konstantopoulou, I, Benítez, J, Friedman, E, Kaufman, B, Laitman, Y, Mai, PL, Greene, MH, Nevanlinna, H, Aittomäki, K, Szabo, CI, Caldes, T, Couch, FJ, Andrulis, IL, Godwin, AK, Hamann, U & Schmutzler, RK 2010, 'Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers', Cancer Epidemiology Biomarkers and Prevention, vol. 19, no. 11, pp. 2859-2868. https://doi.org/10.1158/1055-9965.EPI-10-0517
Engel, Christoph ; Versmold, Beatrix ; Wappenschmidt, Barbara ; Simard, Jacques ; Easton, Douglas F. ; Peock, Susan ; Cook, Margaret ; Oliver, Clare ; Frost, Debra ; Mayes, Rebecca ; Evans, D. Gareth ; Eeles, Rosalind ; Paterson, Joan ; Brewer, Carole ; McGuffog, Lesley ; Antoniou, Antonis C. ; Stoppa-Lyonnet, Dominique ; Sinilnikova, Olga M. ; Barjhoux, Laure ; Frenay, Marc ; Michel, Cécile ; Leroux, Dominique ; Dreyfus, Helene ; Toulas, Christine ; Gladieff, Laurence ; Uhrhammer, Nancy ; Bignon, Yves Jean ; Meindl, Alfons ; Arnold, Norbert ; Varon-Mateeva, Raymonda ; Niederacher, Dieter ; Preisler-Adams, Sabine ; Kast, Karin ; Deissler, Helmut ; Sutter, Christian ; Gadzicki, Dorothea ; Chenevix-Trench, Georgia ; Spurdle, Amanda B. ; Chen, Xiaoqing ; Beesley, Jonathan ; Olsson, Håkan ; Kristoffersson, Ulf ; Ehrencrona, Hans ; 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 ; Ramón Y Cajal, Teresa ; Konstantopoulou, Irene ; Benítez, Javier ; Friedman, Eitan ; Kaufman, Bella ; Laitman, Yael ; Mai, Phuong L. ; Greene, Mark H. ; Nevanlinna, Heli ; Aittomäki, Kristiina ; Szabo, Csilla I. ; Caldes, Trinidad ; Couch, Fergus J ; Andrulis, Irene L. ; Godwin, Andrew K. ; Hamann, Ute ; Schmutzler, Rita K. / Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. In: Cancer Epidemiology Biomarkers and Prevention. 2010 ; Vol. 19, No. 11. pp. 2859-2868.
@article{ea4156ff5e1e4e0c823da4bd55fda2d0,
title = "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; Ptrend = 0.011) and ovarian cancer (per-allele HR, 0.69; 95{\%} CI, 0.53-0.89; Ptrend = 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 riskmodifiers 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.",
author = "Christoph Engel and Beatrix Versmold and Barbara Wappenschmidt and Jacques Simard and Easton, {Douglas F.} and Susan Peock and Margaret Cook and Clare Oliver and Debra Frost and Rebecca Mayes and Evans, {D. Gareth} and Rosalind Eeles and Joan Paterson and Carole Brewer and Lesley McGuffog and Antoniou, {Antonis C.} and Dominique Stoppa-Lyonnet and Sinilnikova, {Olga M.} and Laure Barjhoux and Marc Frenay and C{\'e}cile Michel and Dominique Leroux and Helene Dreyfus and Christine Toulas and Laurence Gladieff and Nancy Uhrhammer and Bignon, {Yves Jean} and Alfons Meindl and Norbert Arnold and Raymonda Varon-Mateeva and Dieter Niederacher and Sabine Preisler-Adams and Karin Kast and Helmut Deissler and Christian Sutter and Dorothea Gadzicki and Georgia Chenevix-Trench and Spurdle, {Amanda B.} and Xiaoqing Chen and Jonathan Beesley and H{\aa}kan Olsson and Ulf Kristoffersson and Hans Ehrencrona and Annelie Liljegren 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 Ana Osorio and {Ram{\'o}n Y Cajal}, Teresa and Irene Konstantopoulou and Javier Ben{\'i}tez and Eitan Friedman and Bella Kaufman and Yael Laitman and Mai, {Phuong L.} and Greene, {Mark H.} and Heli Nevanlinna and Kristiina Aittom{\"a}ki and Szabo, {Csilla I.} and Trinidad Caldes and Couch, {Fergus J} and Andrulis, {Irene L.} and Godwin, {Andrew K.} and Ute Hamann and Schmutzler, {Rita K.}",
year = "2010",
month = "11",
doi = "10.1158/1055-9965.EPI-10-0517",
language = "English (US)",
volume = "19",
pages = "2859--2868",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

AU - Engel, Christoph

AU - Versmold, Beatrix

AU - Wappenschmidt, Barbara

AU - Simard, Jacques

AU - Easton, Douglas F.

AU - Peock, Susan

AU - Cook, Margaret

AU - Oliver, Clare

AU - Frost, Debra

AU - Mayes, Rebecca

AU - Evans, D. Gareth

AU - Eeles, Rosalind

AU - Paterson, Joan

AU - Brewer, Carole

AU - McGuffog, Lesley

AU - Antoniou, Antonis C.

AU - Stoppa-Lyonnet, Dominique

AU - Sinilnikova, Olga M.

AU - Barjhoux, Laure

AU - Frenay, Marc

AU - Michel, Cécile

AU - Leroux, Dominique

AU - Dreyfus, Helene

AU - Toulas, Christine

AU - Gladieff, Laurence

AU - Uhrhammer, Nancy

AU - Bignon, Yves Jean

AU - Meindl, Alfons

AU - Arnold, Norbert

AU - Varon-Mateeva, Raymonda

AU - Niederacher, Dieter

AU - Preisler-Adams, Sabine

AU - Kast, Karin

AU - Deissler, Helmut

AU - Sutter, Christian

AU - Gadzicki, Dorothea

AU - Chenevix-Trench, Georgia

AU - Spurdle, Amanda B.

AU - Chen, Xiaoqing

AU - Beesley, Jonathan

AU - Olsson, Håkan

AU - Kristoffersson, Ulf

AU - Ehrencrona, Hans

AU - Liljegren, Annelie

AU - Van Der Luijt, Rob B.

AU - Van Os, Theo A.

AU - Van Leeuwen, Flora E.

AU - Domchek, Susan M.

AU - Rebbeck, Timothy R.

AU - Nathanson, Katherine L.

AU - Osorio, Ana

AU - Ramón Y Cajal, Teresa

AU - Konstantopoulou, Irene

AU - Benítez, Javier

AU - Friedman, Eitan

AU - Kaufman, Bella

AU - Laitman, Yael

AU - Mai, Phuong L.

AU - Greene, Mark H.

AU - Nevanlinna, Heli

AU - Aittomäki, Kristiina

AU - Szabo, Csilla I.

AU - Caldes, Trinidad

AU - Couch, Fergus J

AU - Andrulis, Irene L.

AU - Godwin, Andrew K.

AU - Hamann, Ute

AU - Schmutzler, Rita K.

PY - 2010/11

Y1 - 2010/11

N2 - 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; Ptrend = 0.011) and ovarian cancer (per-allele HR, 0.69; 95% CI, 0.53-0.89; Ptrend = 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 riskmodifiers 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.

AB - 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; Ptrend = 0.011) and ovarian cancer (per-allele HR, 0.69; 95% CI, 0.53-0.89; Ptrend = 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 riskmodifiers 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.

UR - http://www.scopus.com/inward/record.url?scp=78549237225&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78549237225&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-10-0517

DO - 10.1158/1055-9965.EPI-10-0517

M3 - Article

C2 - 20978178

AN - SCOPUS:78549237225

VL - 19

SP - 2859

EP - 2868

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 11

ER -