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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

Association of the Variants CASP8 D302H and CASP10 V410I with Breast and Ovarian Cancer Risk in... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Epidemiology, Biomarkers & Prevention American Association of Cancer Research

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

Cancer Epidemiology, Biomarkers & Prevention , Volume 19 (11): 2859 – Nov 1, 2010

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.

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References (32)

  • M. Gaudet, Anna-Giulia Fara, I. Beritognolo, M. Sabatti (2009)

    Allele-specific PCR in SNP genotyping.

    Methods in molecular biology, 578

  • J. Son, Hyo-Kyung Kang, M. Chae, J. Choi, J. Park, W. Lee, C. Kim, Dong Kim, S. Kam, Y. Kang, Jae-Yong Park (2006)

    Polymorphisms in the caspase-8 gene and the risk of lung cancer.

    Cancer genetics and cytogenetics, 169 2

  • S. Suela, Eva Cardeñosa, Eva González, Inmaculada Jiménez, I. González, Á. Huerta, C. Ponce, E. Dueñas, Joaquín Salcedo, Victoria Sánchez, P. Gilabert, O. Community (2009)

    CASP8 D302H polymorphism delays the age of onset of breast cancer in BRCA1 and BRCA2 carriers

    Breast Cancer Research and Treatment, 119

  • T. Sun, Yang Gao, W. Tan, Sufang Ma, Yuankai Shi, Jiarui Yao, Yongli Guo, Ming Yang, Xuemei Zhang, Qingrun Zhang, Changqing Zeng, D. Lin (2007)

    A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers

    Nature Genetics, 39

  • R. Siegel (2006)

    Caspases at the crossroads of immune-cell life and death

    Nature Reviews Immunology, 6

  • A. Antoniou, A. Spurdle, O. Sinilnikova, S. Healey, K. Pooley, R. Schmutzler, B. Versmold, C. Engel, A. Meindl, N. Arnold, Wera Hofmann, C. Sutter, D. Niederacher, H. Deissler, T. Caldés, Kati Kämpjärvi, H. Nevanlinna, J. Simard, J. Beesley, Xiaoqing Chen, S. Neuhausen, T. Rebbeck, T. Wagner, Henry Lynch, C. Isaacs, J. Weitzel, Patricia Ganz, M. Daly, G. Tomlinson, O. Olopade, Joanne Blum, F. Couch, P. Peterlongo, S. Manoukian, M. Barile, P. Radice, C. Szabo, Lutecia Pereira, Mark Greene, G. Rennert, F. Lejbkowicz, O. Barnett-Griness, I. Andrulis, H. Ozçelik, A. Gerdes, M. Caligo, Y. Laitman, B. Kaufman, Roni Milgrom, Eitan Friedman, S. Domchek, K. Nathanson, A. Osorio, G. Llort, R. Milne, J. Benítez, U. Hamann, Frans Hogervorst, P. Manders, M. Ligtenberg, A. Ouweland, S. Peock, M. Cook, Radka Platte, D. Evans, R. Eeles, G. Pichert, C. Chu, D. Eccles, R. Davidson, F. Douglas, Andrew Godwin, L. Barjhoux, S. Mazoyer, H. Sobol, V. Bourdon, F. Eisinger, A. Chompret, C. Capoulade, B. Paillerets, Gilbert Lenoir, M. Gauthier‐Villars, C. Houdayer, D. Stoppa-Lyonnet, G. Chenevix-Trench, D. Easton (2008)

    Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers.

    American journal of human genetics, 82 4

  • Hong-Sug Kim, J. Lee, Y. Soung, W. Park, S. Kim, Jong Lee, J. Park, Yong Cho, Chang Kim, Seong-Whan Jeong, S. Nam, S. Kim, Jung Lee, N. Yoo, S. Lee (2003)

    Inactivating mutations of caspase-8 gene in colorectal carcinomas.

    Gastroenterology, 125 3

  • G. Macpherson, S. Catherine, Healey, M. Teare, Sabapathy, P. Balasubramanian, Malcolm, W. Reed, Paul Pharoah, B. Ponder, M. Meuth, Nitai Bhattacharyya, A. Cox (2004)

    Association of a common variant of the CASP8 gene with reduced risk of breast cancer.

    Journal of the National Cancer Institute, 96 24

  • B. Frank, K. Hemminki, B. Wappenschmidt, A. Meindl, R. Klaes, R. Schmutzler, P. Bugert, M. Untch, C. Bartram, B. Burwinkel (2006)

    Association of the CASP10 V410I variant with reduced familial breast cancer risk and interaction with the CASP8 D302H variant.

    Carcinogenesis, 27 3

  • P. Rajaraman, Sophia Wang, N. Rothman, Merideth Brown, P. Black, H. Fine, J. Loeffler, R. Selker, W. Shapiro, S. Chanock, P. Inskip (2007)

    Polymorphisms in Apoptosis and Cell Cycle Control Genes and Risk of Brain Tumors in Adults

    Cancer Epidemiology Biomarkers & Prevention, 16

  • D. Lin, L. Wei (1989)

    The Robust Inference for the Cox Proportional Hazards Model

    Journal of the American Statistical Association, 84

  • S. Ramus, R. Vierkant, S. Johnatty, M. Pike, D. Berg, A. Wu, C. Pearce, U. Menon, A. Gentry-Maharaj, S. Gayther, R. Dicioccio, V. McGuire, A. Whittemore, Honglin Song, D. Easton, P. Pharoah, M. García-Closas, S. Chanock, J. Lissowska, L. Brinton, K. Terry, D. Cramer, S. Tworoger, S. Hankinson, A. Berchuck, P. Moorman, J. Schildkraut, J. Cunningham, M. Liebow, S. Kjaer, E. Høgdall, C. Høgdall, J. Blaakaer, R. Ness, K. Moysich, R. Edwards, M. Carney, G. Lurie, M. Goodman, S. Wang-gohrke, S. Kropp, J. Chang-Claude, P. Webb, Xiaoqing Chen, J. Beesley, G. Chenevix-Trench, E. Goode (2008)

    Consortium analysis of 7 candidate SNPs for ovarian cancer

    International Journal of Cancer, 123

  • Xianshu Wang, V. Pankratz, Z. Fredericksen, R. Tarrell, Mary Karaus, L. McGuffog, P. Pharaoh, B.A.J Ponder, A. Dunning, S. Peock, M. Cook, Clare Oliver, D. Frost, O. Sinilnikova, D. Stoppa-Lyonnet, S. Mazoyer, C. Houdayer, Frans Hogervorst, M. Hooning, M. Ligtenberg, A. Spurdle, G. Chenevix-Trench, R. Schmutzler, B. Wappenschmidt, C. Engel, A. Meindl, S. Domchek, K. Nathanson, T. Rebbeck, Christian Singer, D. Gschwantler-Kaulich, C. Dressler, Anneliese Fink, C. Szabo, M. Zikan, L. Foretova, K. Claes, G. Thomas, R. Hoover, D. Hunter, S. Chanock, D. Easton, A. Antoniou, F. Couch (2010)

    Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers.

    Human molecular genetics, 19 14

  • A. Antoniou, O. Sinilnikova, J. Simard, M. Léoné, M. Dumont, S. Neuhausen, J. Struewing, D. Stoppa-Lyonnet, L. Barjhoux, D. Hughes, I. Coupier, Muriel Belotti, C. Lasset, V. Bonadona, Y. Bignon, T. Rebbeck, T. Wagner, H. Lynch, S. Domchek, K. Nathanson, J. Garber, J. Weitzel, S. Narod, G. Tomlinson, O. Olopade, A. Godwin, C. Isaacs, A. Jakubowska, J. Lubiński, J. Gronwald, B. Górski, T. Byrski, T. Huzarski, S. Peock, M. Cook, C. Baynes, Alexandra Murray, M. Rogers, P. Daly, H. Dorkins, R. Schmutzler, B. Versmold, C. Engel, A. Meindl, N. Arnold, D. Niederacher, H. Deissler, A. Spurdle, Xiaoqing Chen, N. Waddell, N. Cloonan, T. Kirchhoff, K. Offit, E. Friedman, B. Kaufmann, Y. Laitman, G. Galore, G. Rennert, F. Lejbkowicz, L. Raskin, I. Andrulis, E. Ilyushik, H. Ozçelik, P. Devilee, M. Vreeswijk, M. Greene, S. Prindiville, A. Osorio, J. Benítez, M. Zikan, C. Szabo, O. Kilpivaara, H. Nevanlinna, U. Hamann, F. Durocher, A. Arason, F. Couch, D. Easton, G. Chenevix-Trench (2007)

    RAD51 135G-->C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies.

    American journal of human genetics, 81 6

  • A. Antoniou, P. Pharoah, S. Narod, H. Risch, J. Eyfjord, J. Hopper, N. Loman, Hampus Olsson, O. Johannsson, Å. Borg, B. Pasini, P. Radice, S. Manoukian, D. Eccles, N. Tang, E. Oláh, H. Anton-Culver, E. Warner, J. Lubiński, J. Gronwald, B. Górski, H. Tulinius, S. Thorlacius, H. Eerola, H. Nevanlinna, K. Syrjäkoski, O. Kallioniemi, Deborah Thompson, Chris Evans, J. Peto, F. Lalloo, D. Evans, D. Easton (2003)

    Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies.

    American journal of human genetics, 72 5

  • W. Park, Jong Lee, M. Shin, J. Park, Hong-Sug Kim, Jong Lee, Y. Kim, Shi-Nae Lee, Wenhua Xiao, C. Park, S. Lee, N. Yoo, Jung Lee (2002)

    Inactivating mutations of the caspase-10 gene in gastric cancer

    Oncogene, 21

  • G. Chenevix-Trench, R. Milne, A. Antoniou, F. Couch, D. Easton, D. Goldgar (2007)

    An international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA)

    Breast Cancer Research, 9

  • A. Latif, H. Mcburney, S. Roberts, F. Lalloo, A. Howell, D. Evans, W. Newman (2010)

    Breast cancer susceptibility variants alter risk in familial ovarian cancer

    Familial Cancer, 9

  • A. Antoniou, D. Goldgar, N. Andrieu, J. Chang-Claude, R. Brohet, M. Rookus, D. Easton (2005)

    A weighted cohort approach for analysing factors modifying disease risks in carriers of high‐risk susceptibility genes

    Genetic Epidemiology, 29

  • Y. Soung, J. Lee, S. Kim, Jin Jang, Yong-Gyu Park, W. Park, S. Nam, Jung Lee, N. Yoo, S. Lee (2005)

    CASPASE-8 gene is inactivated by somatic mutations in gastric carcinomas.

    Cancer research, 65 3

  • G. Evan, K. Vousden (2001)

    Proliferation, cell cycle and apoptosis in cancer

    Nature, 411

  • M. Hengartner (2000)

    The biochemistry of apoptosis

    Nature, 407

  • A. Antoniou, O. Sinilnikova, L. McGuffog, S. Healey, H. Nevanlinna, T. Heikkinen, J. Simard, A. Spurdle, J. Beesley, Xiaoqing Chen, S. Neuhausen, Y. Ding, F. Couch, Xianshu Wang, Z. Fredericksen, P. Peterlongo, B. Peissel, B. Bonanni, A. Viel, L. Bernard, P. Radice, C. Szabo, L. Foretova, M. Zikan, K. Claes, M. Greene, P. Mai, G. Rennert, F. Lejbkowicz, I. Andrulis, I. Andrulis, H. Ozçelik, G. Glendon, A. Gerdes, M. Thomassen, L. Sunde, M. Caligo, Y. Laitman, T. Kontorovich, Shimrit Cohen, B. Kaufman, B. Kaufman, E. Dagan, R. Baruch, E. Friedman, K. Harbst, Gisela Barbany-Bustinza, Johanna Rantala, H. Ehrencrona, P. Karlsson, S. Domchek, K. Nathanson, A. Osorio, I. Blanco, A. Lasa, J. Benítez, U. Hamann, F. Hogervorst, M. Rookus, J. Collée, P. Devilee, M. Ligtenberg, R. Luijt, C. Aalfs, Q. Waisfisz, J. Wijnen, C. Roozendaal, S. Peock, M. Cook, D. Frost, Clare Oliver, Radka Platte, D. Evans, F. Lalloo, R. Eeles, L. Izatt, R. Davidson, C. Chu, D. Eccles, T. Cole, S. Hodgson, A. Godwin, D. Stoppa-Lyonnet, B. Buecher, Méanie Léoné, B. Paillerets, A. Remenieras, O. Caron, G. Lenoir, N. Sevenet, M. Longy, Sandra Ferrer, F. Prieur, D. Goldgar, A. Miron, E. John, E. John, S. Buys, M. Daly, J. Hopper, M. Terry, Yosuf Yassin, C. Singer, D. Gschwantler-Kaulich, C. Staudigl, T. Hansen, R. Barkardottir, T. Kirchhoff, P. Pal, K. Kosarin, K. Offit, M. Piedmonte, G. Rodriguez, K. Wakeley, J. Boggess, J. Basil, P. Schwartz, S. Blank, A. Toland, M. Montagna, Cinzia Casella, E. Imyanitov, Anna Allavena, R. Schmutzler, B. Versmold, C. Engel, A. Meindl, N. Ditsch, N. Arnold, D. Niederacher, H. Deissler, B. Fiebig, C. Suttner, Ines Schönbuchner, D. Gadzicki, T. Caldés, M. Hoya, K. Pooley, D. Easton, G. Chenevix-Trench (2009)

    Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers.

    Human molecular genetics, 18 22

  • N. Shephard, R. Abo, Sushilaben Rigas, B. Frank, Wei-Yu Lin, I. Brock, Adam Shippen, S. Balasubramanian, M. Reed, C. Bartram, A. Meindl, R. Schmutzler, C. Engel, B. Burwinkel, L. Cannon-Albright, K. Allen-Brady, N. Camp, A. Cox (2009)

    A breast cancer risk haplotype in the caspase-8 gene.

    Cancer research, 69 7

  • E. Imyanitov, K. Hanson, B. Zhivotovsky (2005)

    Polymorphic variations in apoptotic genes and cancer predisposition

    Cell Death and Differentiation, 12

  • B. Frank, J. Bermejo, K. Hemminki, R. Klaes, P. Bugert, B. Wappenschmidt, R. Schmutzler, B. Burwinkel (2005)

    Re: Association of a common variant of the CASP8 gene with reduced risk of breast cancer.

    Journal of the National Cancer Institute, 97 13

  • A. Antoniou, M. Rookus, N. Andrieu, R. Brohet, Jenny Chang-Claude, S. Peock, M. Cook, D. Evans, R. Eeles, Embrace, C. Noguès, L. Faivre, P. Gesta, Genepso, F. Leeuwen, M. Ausems, A. Osorio, Geo-Hebon, T. Caldés, J. Simard, J. Lubiński, A. Gerdes, E. Oláh, C. Fuerhauser, H. Olsson, B. Arver, P. Radice, D. Easton, D. Goldgar (2009)

    Reproductive and Hormonal Factors, and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers: Results from the International BRCA1/2 Carrier Cohort Study

    Cancer Epidemiology Biomarkers & Prevention, 18

  • Q. Lan, T. Zheng, S. Chanock, Yawei Zhang, M. Shen, Sophia Wang, S. Berndt, S. Zahm, T. Holford, B. Leaderer, M. Yeager, R. Welch, D. Hosgood, P. Boyle, N. Rothman (2006)

    Genetic variants in caspase genes and susceptibility to non-Hodgkin lymphoma.

    Carcinogenesis, 28 4

  • D. Milhas, O. Cuvillier, N. Therville, Patricia Clavé, M. Thomsen, T. Levade, H. Benoist, B. Ségui (2005)

    Caspase-10 Triggers Bid Cleavage and Caspase Cascade Activation in FasL-induced Apoptosis*

    Journal of Biological Chemistry, 280

  • M. Gaudet, R. Milne, A. Cox, N. Camp, E. Goode, Manjeet Humphreys, A. Dunning, J. Morrison, G. Giles, G. Severi, L. Baglietto, D. English, F. Couch, J. Olson, Xianshu Wang, J. Chang-Claude, D. Flesch-Janys, S. Abbas, R. Salazar, A. Mannermaa, V. Kataja, V. Kosma, A. Lindblom, S. Margolin, T. Heikkinen, Kati Kämpjärvi, Kirsimari Aaltonen, H. Nevanlinna, N. Bogdanova, Irina Coinac, P. Schürmann, T. Dörk, C. Bartram, R. Schmutzler, S. Tchatchou, B. Burwinkel, H. Brauch, Diana Torres, U. Hamann, C. Justenhoven, G. Ribas, J. Arias, J. Benítez, S. Bojesen, B. Nordestgaard, H. Flyger, J. Peto, O. Fletcher, N. Johnson, I. Silva, P. Fasching, M. Beckmann, R. Strick, A. Ekici, A. Broeks, M. Schmidt, F. Leeuwen, L. Veer, M. Southey, J. Hopper, C. Apicella, C. Haiman, B. Henderson, L. Marchand, L. Kolonel, V. Kristensen, Grethe Alnæs, D. Hunter, P. Kraft, D. Cox, S. Hankinson, C. Seynaeve, M. Vreeswijk, R. Tollenaar, P. Devilee, S. Chanock, J. Lissowska, L. Brinton, B. Pepłońska, K. Czene, P. Hall, Yuqing Li, Jianjun Liu, S. Balasubramanian, S. Rafii, M. Reed, K. Pooley, Don Conroy, C. Baynes, D. Kang, K. Yoo, D. Noh, S. Ahn, Chen-Yang Shen, Hui-Chun Wang, Jyh‐cherng Yu, Pei‐Ei Wu, H. Anton-Culver, Argyrios Ziogoas, K. Egan, P. Newcomb, L. Titus-Ernstoff, Amy Dietz, A. Sigurdson, B. Alexander, P. Bhatti, K. Allen-Brady, L. Cannon-Albright, Jathine Wong, G. Chenevix-Trench, A. Spurdle, J. Beesley, P. Pharoah, D. Easton, M. García-Closas (2009)

    Five Polymorphisms and Breast Cancer Risk: Results from the Breast Cancer Association Consortium

    Cancer Epidemiology Biomarkers & Prevention, 18

  • A. Cox, A. Dunning, M. García-Closas, S. Balasubramanian, M. Reed, K. Pooley, S. Scollen, C. Baynes, B. Ponder, S. Chanock, J. Lissowska, L. Brinton, B. Pepłońska, M. Southey, J. Hopper, M. Mccredie, G. Giles, O. Fletcher, N. Johnson, I. Silva, L. Gibson, S. Bojesen, B. Nordestgaard, C. Axelsson, Diana Torres, U. Hamann, C. Justenhoven, H. Brauch, J. Chang-Claude, S. Kropp, A. Risch, S. Wang-gohrke, P. Schürmann, N. Bogdanova, T. Dörk, R. Fagerholm, Kirsimari Aaltonen, C. Blomqvist, H. Nevanlinna, S. Seal, A. Renwick, M. Stratton, N. Rahman, S. Sangrajrang, D. Hughes, F. Odefrey, P. Brennan, A. Spurdle, G. Chenevix-Trench, J. Beesley, A. Mannermaa, J. Hartikainen, V. Kataja, V. Kosma, F. Couch, J. Olson, E. Goode, A. Broeks, M. Schmidt, F. Hogervorst, L. Veer, D. Kang, K. Yoo, D. Noh, S. Ahn, S. Wedrén, P. Hall, Y. Low, Jianjun Liu, R. Milne, G. Ribas, A. González-Neira, J. Benítez, A. Sigurdson, Denise Stredrick, B. Alexander, J. Struewing, P. Pharoah, D. Easton (2007)

    A common coding variant in CASP8 is associated with breast cancer risk

    Nature Genetics, 39

  • B. Frank, Sushilaben Rigas, J. Bermejo, M. Wiestler, Kerstin Wagner, K. Hemminki, M. Reed, C. Sutter, B. Wappenschmidt, S. Balasubramanian, A. Meindl, M. Kiechle, P. Bugert, R. Schmutzler, C. Bartram, C. Justenhoven, Y. Ko, T. Brüning, H. Brauch, U. Hamann, P. Pharoah, A. Dunning, K. Pooley, D. Easton, A. Cox, B. Burwinkel (2008)

    The CASP8 -652 6N del promoter polymorphism and breast cancer risk: a multicenter study

    Breast Cancer Research and Treatment, 111

Publisher
American Association of Cancer Research
Copyright
Copyright © 2010 American Association for Cancer Research
ISSN
1078-0432
eISSN
1538-7755
DOI
10.1158/1055-9965.EPI-10-0517
pmid
20978178
Publisher site
See Article on Publisher Site

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.

Journal

Cancer Epidemiology, Biomarkers & PreventionAmerican Association of Cancer Research

Published: Nov 1, 2010

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