Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

Lin Wei-Yu Lin; Nicola J. Camp; Maya Ghoussaini; Jonathan Beesley; Kyriaki Michailidou; John L. Hopper; Carmel Apicella; Melissa C. Southey; Jennifer Stone; Marjanka K. Schmidt; Annegien Broeks; Laura J. Van't Veer; Emiel J. Th Rutgers; Kenneth Muir; Artitaya Lophatananon; Sarah Stewart-Brown; Pornthep Siriwanarangsan; Peter A. Fasching; Lothar Haeberle; Arif B. Ekici; Matthias W. Beckmann; Julian Peto; Isabel Dos-Santos-Silva; Olivia Fletcher; Nichola Johnson; Manjeet K. Bolla; Qin Wang; Joe Dennis; Elinor J. Sawyer; Timothy Cheng; Ian Tomlinson; Michael J. Kerin; Nicola Miller; Marmé Frederik Marmé; Harald M. Surowy; Barbara Burwinkel; Pascal Guénel; Thérèse Truong; Florence Menegaux; Claire Mulot; Stig E. Bojesen; Børge G. Nordestgaard; Sune F. Nielsen; Henrik Flyger; Javier Benitez; M. Pilar Zamora; Jose Ignacio Arias Perez; Primitiva Menéndez; Anna González-Neira; Guillermo Pita; M. Rosario Alonso; Nuria Álvarez; Daniel Herrero; Hoda Anton-Culver; Hermann Brenner; Aida Karina Dieffenbach; Volker Arndt; Christa Stegmaier; Alfons Meindl; Peter Lichtner; Rita K. Schmutzler; Bertram Müller-Myhsok; Hiltrud Brauch; Thomas Brüning; Yon Dschun Ko; Daniel C. Tessier; Daniel Vincent; Francois Bacot; Heli Nevanlinna; Kristiina Aittomäki; Carl Blomqvist; Sofia Khan; Keitaro Matsuo; Hidemi Ito; Hiroji Iwata; Akiyo Horio; Natalia V. Bogdanova; Natalia N. Antonenkova; Thilo Dörk; Annika Lindblom; Sara Margolin; Arto Mannermaa; Vesa Kataja; Veli Matti Kosma; Jaana M. Hartikainen; Anna H. Wu; Chiu Chen Tseng; David Van Den Berg; Daniel O. Stram; Patrick Neven; Els Wauters; Hans Wildiers; Diether Lambrechts; Jenny Chang-Claude; Anja Rudolph; Petra Seibold; Dieter Flesch-Janys; Paolo Radice; Paolo Peterlongo; Siranoush Manoukian; Bernardo Bonanni; Fergus J. Couch; Xianshu Wang; Celine Vachon; Kristen Purrington; Graham G. Giles; Roger L. Milne; Catriona Mclean; Christopher A. Haiman; Brian E. Henderson; Fredrick Schumacher; Loic Le Marchand; Jacques Simard; Mark S. Goldberg; France Labrèche; Martine Dumont; Soo Hwang Teo; Cheng Har Yip; Norhashimah Hassan; Eranga Nishanthie Vithana; Vessela Kristensen; Wei Zheng; Sandra Deming-Halverson; Martha J. Shrubsole; Jirong Long; Robert Winqvist; Katri Pylkäs; Arja Jukkola-Vuorinen; Saila Kauppila; Irene L. Andrulis; Julia A. Knight; Gord Glendon; Sandrine Tchatchou; Peter Devilee; Robert A E M Tollenaar; Caroline Seynaeve; Christi J. Van Asperen; Montserrat García-Closas; Jonine Figueroa; Jolanta Lissowska; Louise Brinton; Kamila Czene; Hatef Darabi; Mikael Eriksson; Judith S. Brand; Maartje J. Hooning; Antoinette Hollestelle; Ans M W Van DenOuweland; Agnes Jager; Jingmei Li; Jianjun Liu; Keith Humphreys; Xiao Ou Shu; Wei Lu; Yu Tang Gao; Hui Cai; Simon S. Cross; Malcolm W R Reed; William Blot; Lisa B. Signorello; Qiuyin Cai; Paul D P Pharoah; Barbara Perkins; Mitul Shah; Fiona M. Blows; Daehee Kang; Keun Young Yoo; Dong Young Noh; Mikael Hartman; Hui Miao; Kee Seng Chia; Thomas Choudary Putti; Ute Hamann; Craig Luccarini; Caroline Baynes; Shahana Ahmed; Mel Maranian; Catherine S. Healey; Anna Jakubowska; Jan Lubinski; Katarzyna Jaworska-Bieniek; Katarzyna Durda; Suleeporn Sangrajrang; Valerie Gaborieau; Paul Brennan; James Mckay; Susan Slager; Amanda E. Toland; Drakoulis Yannoukakos; Chen Yang Shen; Chia Ni Hsiung; Pei Ei Wu; Shian Ling Ding; Alan Ashworth; Michael Jones; Nick Orr; Anthony J. Swerdlow; Helen Tsimiklis; Enes Makalic; Daniel F. Schmidt; Quang M. Bui; Stephen J. Chanock; David J. Hunter; Rebecca Hein; Norbert Dahmen; Lars Beckmann; Kirsimari Aaltonen; Taru A. Muranen; Tuomas Heikkinen; Astrid Irwanto; Nazneen Rahman; Clare A. Turnbull; Quinten Waisfisz; Hanne E J Meijers-Heijboer; Muriel A. Adank; Rob B. Van Der Luijt; Per Hall; Georgia Chenevix-Trench; Alison Dunning; Douglas F. Easton; Angela Cox

doi:10.1093/hmg/ddu431

Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

Lin Wei-Yu Lin, Nicola J. Camp, Maya Ghoussaini, Jonathan Beesley, Kyriaki Michailidou, John L. Hopper, Carmel Apicella, Melissa C. Southey, Jennifer Stone, Marjanka K. Schmidt, Annegien Broeks, Laura J. Van't Veer, Emiel J. Th Rutgers, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Peter A. Fasching, Lothar Haeberle, Arif B. EkiciMatthias W. Beckmann, Julian Peto, Isabel Dos-Santos-Silva, Olivia Fletcher, Nichola Johnson, Manjeet K. Bolla, Qin Wang, Joe Dennis, Elinor J. Sawyer, Timothy Cheng, Ian Tomlinson, Michael J. Kerin, Nicola Miller, Marmé Frederik Marmé, Harald M. Surowy, Barbara Burwinkel, Pascal Guénel, Thérèse Truong, Florence Menegaux, Claire Mulot, Stig E. Bojesen, Børge G. Nordestgaard, Sune F. Nielsen, Henrik Flyger, Javier Benitez, M. Pilar Zamora, Jose Ignacio Arias Perez, Primitiva Menéndez, Anna González-Neira, Guillermo Pita, M. Rosario Alonso, Nuria Álvarez, Daniel Herrero, Hoda Anton-Culver, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Alfons Meindl, Peter Lichtner, Rita K. Schmutzler, Bertram Müller-Myhsok, Hiltrud Brauch, Thomas Brüning, Yon Dschun Ko, Daniel C. Tessier, Daniel Vincent, Francois Bacot, Heli Nevanlinna, Kristiina Aittomäki, Carl Blomqvist, Sofia Khan, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Akiyo Horio, Natalia V. Bogdanova, Natalia N. Antonenkova, Thilo Dörk, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli Matti Kosma, Jaana M. Hartikainen, Anna H. Wu, Chiu Chen Tseng, David Van Den Berg, Daniel O. Stram, Patrick Neven, Els Wauters, Hans Wildiers, Diether Lambrechts, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Bernardo Bonanni, Fergus J. Couch, Xianshu Wang, Celine Vachon, Kristen Purrington, Graham G. Giles, Roger L. Milne, Catriona Mclean, Christopher A. Haiman, Brian E. Henderson, Fredrick Schumacher, Loic Le Marchand, Jacques Simard, Mark S. Goldberg, France Labrèche, Martine Dumont, Soo Hwang Teo, Cheng Har Yip, Norhashimah Hassan, Eranga Nishanthie Vithana, Vessela Kristensen, Wei Zheng, Sandra Deming-Halverson, Martha J. Shrubsole, Jirong Long, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Saila Kauppila, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Sandrine Tchatchou, Peter Devilee, Robert A E M Tollenaar, Caroline Seynaeve, Christi J. Van Asperen, Montserrat García-Closas, Jonine Figueroa, Jolanta Lissowska, Louise Brinton, Kamila Czene, Hatef Darabi, Mikael Eriksson, Judith S. Brand, Maartje J. Hooning, Antoinette Hollestelle, Ans M W Van DenOuweland, Agnes Jager, Jingmei Li, Jianjun Liu, Keith Humphreys, Xiao Ou Shu, Wei Lu, Yu Tang Gao, Hui Cai, Simon S. Cross, Malcolm W R Reed, William Blot, Lisa B. Signorello, Qiuyin Cai, Paul D P Pharoah, Barbara Perkins, Mitul Shah, Fiona M. Blows, Daehee Kang, Keun Young Yoo, Dong Young Noh, Mikael Hartman, Hui Miao, Kee Seng Chia, Thomas Choudary Putti, Ute Hamann, Craig Luccarini, Caroline Baynes, Shahana Ahmed, Mel Maranian, Catherine S. Healey, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James Mckay, Susan Slager, Amanda E. Toland, Drakoulis Yannoukakos, Chen Yang Shen, Chia Ni Hsiung, Pei Ei Wu, Shian Ling Ding, Alan Ashworth, Michael Jones, Nick Orr, Anthony J. Swerdlow, Helen Tsimiklis, Enes Makalic, Daniel F. Schmidt, Quang M. Bui, Stephen J. Chanock, David J. Hunter, Rebecca Hein, Norbert Dahmen, Lars Beckmann, Kirsimari Aaltonen, Taru A. Muranen, Tuomas Heikkinen, Astrid Irwanto, Nazneen Rahman, Clare A. Turnbull, Quinten Waisfisz, Hanne E J Meijers-Heijboer, Muriel A. Adank, Rob B. Van Der Luijt, Per Hall, Georgia Chenevix-Trench, Alison Dunning, Douglas F. Easton, Angela Cox^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

2 Citations (Scopus)

Abstract

Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10-5. Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P=3 × 10-6), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10-9. Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8might be the target gene, suggesting amechanism involving apoptosis.

Original language	English
Pages (from-to)	285-298
Number of pages	14
Journal	Human Molecular Genetics
Volume	24
Issue number	1
DOIs	https://doi.org/10.1093/hmg/ddu431
Publication status	Published - 1 Jan 2015

Access to Document

10.1093/hmg/ddu431

Cite this

Wei-Yu Lin, L., Camp, N. J., Ghoussaini, M., Beesley, J., Michailidou, K., Hopper, J. L., Apicella, C., Southey, M. C., Stone, J., Schmidt, M. K., Broeks, A., Van't Veer, L. J., Th Rutgers, E. J., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Fasching, P. A., Haeberle, L., ... Cox, A. (2015). Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk. Human Molecular Genetics, 24(1), 285-298. https://doi.org/10.1093/hmg/ddu431

@article{35cbf6b38561409797806a45e6f26af4,

title = "Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk",

abstract = "Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10-5. Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P=3 × 10-6), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10-9. Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8might be the target gene, suggesting amechanism involving apoptosis.",

author = "{Wei-Yu Lin}, Lin and Camp, {Nicola J.} and Maya Ghoussaini and Jonathan Beesley and Kyriaki Michailidou and Hopper, {John L.} and Carmel Apicella and Southey, {Melissa C.} and Jennifer Stone and Schmidt, {Marjanka K.} and Annegien Broeks and {Van't Veer}, {Laura J.} and {Th Rutgers}, {Emiel J.} and Kenneth Muir and Artitaya Lophatananon and Sarah Stewart-Brown and Pornthep Siriwanarangsan and Fasching, {Peter A.} and Lothar Haeberle and Ekici, {Arif B.} and Beckmann, {Matthias W.} and Julian Peto and Isabel Dos-Santos-Silva and Olivia Fletcher and Nichola Johnson and Bolla, {Manjeet K.} and Qin Wang and Joe Dennis and Sawyer, {Elinor J.} and Timothy Cheng and Ian Tomlinson and Kerin, {Michael J.} and Nicola Miller and {Frederik Marm{\'e}}, Marm{\'e} and Surowy, {Harald M.} and Barbara Burwinkel and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Florence Menegaux and Claire Mulot and Bojesen, {Stig E.} and Nordestgaard, {B{\o}rge G.} and Nielsen, {Sune F.} and Henrik Flyger and Javier Benitez and {Pilar Zamora}, M. and Perez, {Jose Ignacio Arias} and Primitiva Men{\'e}ndez and Anna Gonz{\'a}lez-Neira and Guillermo Pita and {Rosario Alonso}, M. and Nuria {\'A}lvarez and Daniel Herrero and Hoda Anton-Culver and Hermann Brenner and Dieffenbach, {Aida Karina} and Volker Arndt and Christa Stegmaier and Alfons Meindl and Peter Lichtner and Schmutzler, {Rita K.} and Bertram M{\"u}ller-Myhsok and Hiltrud Brauch and Thomas Br{\"u}ning and Ko, {Yon Dschun} and Tessier, {Daniel C.} and Daniel Vincent and Francois Bacot and Heli Nevanlinna and Kristiina Aittom{\"a}ki and Carl Blomqvist and Sofia Khan and Keitaro Matsuo and Hidemi Ito and Hiroji Iwata and Akiyo Horio and Bogdanova, {Natalia V.} and Antonenkova, {Natalia N.} and Thilo D{\"o}rk and Annika Lindblom and Sara Margolin and Arto Mannermaa and Vesa Kataja and Kosma, {Veli Matti} and Hartikainen, {Jaana M.} and Wu, {Anna H.} and Tseng, {Chiu Chen} and {Van Den Berg}, David and Stram, {Daniel O.} and Patrick Neven and Els Wauters and Hans Wildiers and Diether Lambrechts and Jenny Chang-Claude and Anja Rudolph and Petra Seibold and Dieter Flesch-Janys and Paolo Radice and Paolo Peterlongo and Siranoush Manoukian and Bernardo Bonanni and Couch, {Fergus J.} and Xianshu Wang and Celine Vachon and Kristen Purrington and Giles, {Graham G.} and Milne, {Roger L.} and Catriona Mclean and Haiman, {Christopher A.} and Henderson, {Brian E.} and Fredrick Schumacher and Marchand, {Loic Le} and Jacques Simard and Goldberg, {Mark S.} and France Labr{\`e}che and Martine Dumont and Teo, {Soo Hwang} and Yip, {Cheng Har} and Norhashimah Hassan and Vithana, {Eranga Nishanthie} and Vessela Kristensen and Wei Zheng and Sandra Deming-Halverson and Shrubsole, {Martha J.} and Jirong Long and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Saila Kauppila and Andrulis, {Irene L.} and Knight, {Julia A.} and Gord Glendon and Sandrine Tchatchou and Peter Devilee and Tollenaar, {Robert A E M} and Caroline Seynaeve and {Van Asperen}, {Christi J.} and Montserrat Garc{\'i}a-Closas and Jonine Figueroa and Jolanta Lissowska and Louise Brinton and Kamila Czene and Hatef Darabi and Mikael Eriksson and Brand, {Judith S.} and Hooning, {Maartje J.} and Antoinette Hollestelle and {Van DenOuweland}, {Ans M W} and Agnes Jager and Jingmei Li and Jianjun Liu and Keith Humphreys and Shu, {Xiao Ou} and Wei Lu and Gao, {Yu Tang} and Hui Cai and Cross, {Simon S.} and Reed, {Malcolm W R} and William Blot and Signorello, {Lisa B.} and Qiuyin Cai and Pharoah, {Paul D P} and Barbara Perkins and Mitul Shah and Blows, {Fiona M.} and Daehee Kang and Yoo, {Keun Young} and Noh, {Dong Young} and Mikael Hartman and Hui Miao and Chia, {Kee Seng} and Putti, {Thomas Choudary} and Ute Hamann and Craig Luccarini and Caroline Baynes and Shahana Ahmed and Mel Maranian and Healey, {Catherine S.} and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska-Bieniek and Katarzyna Durda and Suleeporn Sangrajrang and Valerie Gaborieau and Paul Brennan and James Mckay and Susan Slager and Toland, {Amanda E.} and Drakoulis Yannoukakos and Shen, {Chen Yang} and Hsiung, {Chia Ni} and Wu, {Pei Ei} and Ding, {Shian Ling} and Alan Ashworth and Michael Jones and Nick Orr and Swerdlow, {Anthony J.} and Helen Tsimiklis and Enes Makalic and Schmidt, {Daniel F.} and Bui, {Quang M.} and Chanock, {Stephen J.} and Hunter, {David J.} and Rebecca Hein and Norbert Dahmen and Lars Beckmann and Kirsimari Aaltonen and Muranen, {Taru A.} and Tuomas Heikkinen and Astrid Irwanto and Nazneen Rahman and Turnbull, {Clare A.} and Quinten Waisfisz and Meijers-Heijboer, {Hanne E J} and Adank, {Muriel A.} and {Van Der Luijt}, {Rob B.} and Per Hall and Georgia Chenevix-Trench and Alison Dunning and Easton, {Douglas F.} and Angela Cox",

year = "2015",

month = jan,

day = "1",

doi = "10.1093/hmg/ddu431",

language = "English",

volume = "24",

pages = "285--298",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "1",

}

Wei-Yu Lin, L, Camp, NJ, Ghoussaini, M, Beesley, J, Michailidou, K, Hopper, JL, Apicella, C, Southey, MC, Stone, J, Schmidt, MK, Broeks, A, Van't Veer, LJ, Th Rutgers, EJ, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Peto, J, Dos-Santos-Silva, I, Fletcher, O, Johnson, N, Bolla, MK, Wang, Q, Dennis, J, Sawyer, EJ, Cheng, T, Tomlinson, I, Kerin, MJ, Miller, N, Frederik Marmé, M, Surowy, HM, Burwinkel, B, Guénel, P, Truong, T, Menegaux, F, Mulot, C, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Benitez, J, Pilar Zamora, M, Perez, JIA, Menéndez, P, González-Neira, A, Pita, G, Rosario Alonso, M, Álvarez, N, Herrero, D, Anton-Culver, H, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Meindl, A, Lichtner, P, Schmutzler, RK, Müller-Myhsok, B, Brauch, H, Brüning, T, Ko, YD, Tessier, DC, Vincent, D, Bacot, F, Nevanlinna, H, Aittomäki, K, Blomqvist, C, Khan, S, Matsuo, K, Ito, H, Iwata, H, Horio, A, Bogdanova, NV, Antonenkova, NN, Dörk, T, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, JM, Wu, AH, Tseng, CC, Van Den Berg, D, Stram, DO, Neven, P, Wauters, E, Wildiers, H, Lambrechts, D, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Bonanni, B, Couch, FJ, Wang, X, Vachon, C, Purrington, K, Giles, GG, Milne, RL, Mclean, C, Haiman, CA, Henderson, BE, Schumacher, F, Marchand, LL, Simard, J, Goldberg, MS, Labrèche, F, Dumont, M, Teo, SH, Yip, CH, Hassan, N, Vithana, EN, Kristensen, V, Zheng, W, Deming-Halverson, S, Shrubsole, MJ, Long, J, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Kauppila, S, Andrulis, IL, Knight, JA, Glendon, G, Tchatchou, S, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Van Asperen, CJ, García-Closas, M, Figueroa, J, Lissowska, J, Brinton, L, Czene, K, Darabi, H, Eriksson, M, Brand, JS, Hooning, MJ, Hollestelle, A, Van DenOuweland, AMW, Jager, A, Li, J, Liu, J, Humphreys, K, Shu, XO, Lu, W, Gao, YT, Cai, H, Cross, SS, Reed, MWR, Blot, W, Signorello, LB, Cai, Q, Pharoah, PDP, Perkins, B, Shah, M, Blows, FM, Kang, D, Yoo, KY, Noh, DY, Hartman, M, Miao, H, Chia, KS, Putti, TC, Hamann, U, Luccarini, C, Baynes, C, Ahmed, S, Maranian, M, Healey, CS, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Slager, S, Toland, AE, Yannoukakos, D, Shen, CY, Hsiung, CN, Wu, PE, Ding, SL, Ashworth, A, Jones, M, Orr, N, Swerdlow, AJ, Tsimiklis, H, Makalic, E, Schmidt, DF, Bui, QM, Chanock, SJ, Hunter, DJ, Hein, R, Dahmen, N, Beckmann, L, Aaltonen, K, Muranen, TA, Heikkinen, T, Irwanto, A, Rahman, N, Turnbull, CA, Waisfisz, Q, Meijers-Heijboer, HEJ, Adank, MA, Van Der Luijt, RB, Hall, P, Chenevix-Trench, G, Dunning, A, Easton, DF & Cox, A 2015, 'Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk', Human Molecular Genetics, vol. 24, no. 1, pp. 285-298. https://doi.org/10.1093/hmg/ddu431

TY - JOUR

T1 - Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

AU - Wei-Yu Lin, Lin

AU - Camp, Nicola J.

AU - Ghoussaini, Maya

AU - Beesley, Jonathan

AU - Michailidou, Kyriaki

AU - Hopper, John L.

AU - Apicella, Carmel

AU - Southey, Melissa C.

AU - Stone, Jennifer

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Van't Veer, Laura J.

AU - Th Rutgers, Emiel J.

AU - Muir, Kenneth

AU - Lophatananon, Artitaya

AU - Stewart-Brown, Sarah

AU - Siriwanarangsan, Pornthep

AU - Fasching, Peter A.

AU - Haeberle, Lothar

AU - Ekici, Arif B.

AU - Beckmann, Matthias W.

AU - Peto, Julian

AU - Dos-Santos-Silva, Isabel

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Dennis, Joe

AU - Sawyer, Elinor J.

AU - Cheng, Timothy

AU - Tomlinson, Ian

AU - Kerin, Michael J.

AU - Miller, Nicola

AU - Frederik Marmé, Marmé

AU - Surowy, Harald M.

AU - Burwinkel, Barbara

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - Menegaux, Florence

AU - Mulot, Claire

AU - Bojesen, Stig E.

AU - Nordestgaard, Børge G.

AU - Nielsen, Sune F.

AU - Flyger, Henrik

AU - Benitez, Javier

AU - Pilar Zamora, M.

AU - Perez, Jose Ignacio Arias

AU - Menéndez, Primitiva

AU - González-Neira, Anna

AU - Pita, Guillermo

AU - Rosario Alonso, M.

AU - Álvarez, Nuria

AU - Herrero, Daniel

AU - Anton-Culver, Hoda

AU - Brenner, Hermann

AU - Dieffenbach, Aida Karina

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Meindl, Alfons

AU - Lichtner, Peter

AU - Schmutzler, Rita K.

AU - Müller-Myhsok, Bertram

AU - Brauch, Hiltrud

AU - Brüning, Thomas

AU - Ko, Yon Dschun

AU - Tessier, Daniel C.

AU - Vincent, Daniel

AU - Bacot, Francois

AU - Nevanlinna, Heli

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Khan, Sofia

AU - Matsuo, Keitaro

AU - Ito, Hidemi

AU - Iwata, Hiroji

AU - Horio, Akiyo

AU - Bogdanova, Natalia V.

AU - Antonenkova, Natalia N.

AU - Dörk, Thilo

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli Matti

AU - Hartikainen, Jaana M.

AU - Wu, Anna H.

AU - Tseng, Chiu Chen

AU - Van Den Berg, David

AU - Stram, Daniel O.

AU - Neven, Patrick

AU - Wauters, Els

AU - Wildiers, Hans

AU - Lambrechts, Diether

AU - Chang-Claude, Jenny

AU - Rudolph, Anja

AU - Seibold, Petra

AU - Flesch-Janys, Dieter

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Bonanni, Bernardo

AU - Couch, Fergus J.

AU - Wang, Xianshu

AU - Vachon, Celine

AU - Purrington, Kristen

AU - Giles, Graham G.

AU - Milne, Roger L.

AU - Mclean, Catriona

AU - Haiman, Christopher A.

AU - Henderson, Brian E.

AU - Schumacher, Fredrick

AU - Marchand, Loic Le

AU - Simard, Jacques

AU - Goldberg, Mark S.

AU - Labrèche, France

AU - Dumont, Martine

AU - Teo, Soo Hwang

AU - Yip, Cheng Har

AU - Hassan, Norhashimah

AU - Vithana, Eranga Nishanthie

AU - Kristensen, Vessela

AU - Zheng, Wei

AU - Deming-Halverson, Sandra

AU - Shrubsole, Martha J.

AU - Long, Jirong

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Kauppila, Saila

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Glendon, Gord

AU - Tchatchou, Sandrine

AU - Devilee, Peter

AU - Tollenaar, Robert A E M

AU - Seynaeve, Caroline

AU - Van Asperen, Christi J.

AU - García-Closas, Montserrat

AU - Figueroa, Jonine

AU - Lissowska, Jolanta

AU - Brinton, Louise

AU - Czene, Kamila

AU - Darabi, Hatef

AU - Eriksson, Mikael

AU - Brand, Judith S.

AU - Hooning, Maartje J.

AU - Hollestelle, Antoinette

AU - Van DenOuweland, Ans M W

AU - Jager, Agnes

AU - Li, Jingmei

AU - Liu, Jianjun

AU - Humphreys, Keith

AU - Shu, Xiao Ou

AU - Lu, Wei

AU - Gao, Yu Tang

AU - Cai, Hui

AU - Cross, Simon S.

AU - Reed, Malcolm W R

AU - Blot, William

AU - Signorello, Lisa B.

AU - Cai, Qiuyin

AU - Pharoah, Paul D P

AU - Perkins, Barbara

AU - Shah, Mitul

AU - Blows, Fiona M.

AU - Kang, Daehee

AU - Yoo, Keun Young

AU - Noh, Dong Young

AU - Hartman, Mikael

AU - Miao, Hui

AU - Chia, Kee Seng

AU - Putti, Thomas Choudary

AU - Hamann, Ute

AU - Luccarini, Craig

AU - Baynes, Caroline

AU - Ahmed, Shahana

AU - Maranian, Mel

AU - Healey, Catherine S.

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Jaworska-Bieniek, Katarzyna

AU - Durda, Katarzyna

AU - Sangrajrang, Suleeporn

AU - Gaborieau, Valerie

AU - Brennan, Paul

AU - Mckay, James

AU - Slager, Susan

AU - Toland, Amanda E.

AU - Yannoukakos, Drakoulis

AU - Shen, Chen Yang

AU - Hsiung, Chia Ni

AU - Wu, Pei Ei

AU - Ding, Shian Ling

AU - Ashworth, Alan

AU - Jones, Michael

AU - Orr, Nick

AU - Swerdlow, Anthony J.

AU - Tsimiklis, Helen

AU - Makalic, Enes

AU - Schmidt, Daniel F.

AU - Bui, Quang M.

AU - Chanock, Stephen J.

AU - Hunter, David J.

AU - Hein, Rebecca

AU - Dahmen, Norbert

AU - Beckmann, Lars

AU - Aaltonen, Kirsimari

AU - Muranen, Taru A.

AU - Heikkinen, Tuomas

AU - Irwanto, Astrid

AU - Rahman, Nazneen

AU - Turnbull, Clare A.

AU - Waisfisz, Quinten

AU - Meijers-Heijboer, Hanne E J

AU - Adank, Muriel A.

AU - Van Der Luijt, Rob B.

AU - Hall, Per

AU - Chenevix-Trench, Georgia

AU - Dunning, Alison

AU - Easton, Douglas F.

AU - Cox, Angela

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10-5. Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P=3 × 10-6), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10-9. Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8might be the target gene, suggesting amechanism involving apoptosis.

AB - Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10-5. Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P=3 × 10-6), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10-9. Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8might be the target gene, suggesting amechanism involving apoptosis.

UR - http://www.scopus.com/inward/record.url?scp=84927610980&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddu431

DO - 10.1093/hmg/ddu431

M3 - Article

C2 - 25168388

AN - SCOPUS:84927610980

SN - 0964-6906

VL - 24

SP - 285

EP - 298

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 1

ER -

Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

Abstract

Access to Document

Other files and links

Fingerprint

Cite this