Common non-synonymous SNPs associated with breast cancer susceptibility

Findings from the Breast Cancer Association Consortium

Roger L. Milne, Barbara Burwinkel, Kyriaki Michailidou, Jose Ignacio Arias Perez, M. Pilar Zamora, Primitiva Menéndez-Rodríguez, David Hardisson, Marta Mendiola, Anna González-Neira, Guillermo Pita, M. Rosario Alonso, Joe Dennis, Qin Wang, Manjeet K. Bolla, Anthony Swerdlow, Alan Ashworth, Nick Orr, Minouk Schoemaker, Yon Dschun Ko, Hiltrud Brauch & 157 others Ute Hamann, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Sandrine Tchatchou, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Kazuo Tajima, Jingmei Li, Judith S. Brand, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Diether Lambrechts, Gilian Peuteman, Marie Rose Christiaens, Ann Smeets, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska-Bieniek, Katazyna Durda, Mikael Hartman, Miao Hui, Wei Yen Lim, Ching Wan Chan, Federick Marme, Rongxi Yang, Peter Bugert, Annika Lindblom, Sara Margolin, Montserrat García-Closas, Stephen J. Chanock, Jolanta Lissowska, Jonine D. Figueroa, Stig E. Bojesen, Børge G. Nordestgaard, Henrik Flyger, Maartje J. Hooning, Mieke Kriege, Ans M W van den Ouweland, Linetta B. Koppert, Olivia Fletcher, Nichola Johnson, Isabel dos-Santos-Silva, Julian Peto, Wei Zheng, Sandra Deming-Halverson, Martha J. Shrubsole, Jirong Long, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Angela Cox, Simon S. Cross, Malcolm W R Reed, Marjanka K. Schmidt, Annegien Broeks, Sten Cornelissen, Linde Braaf, Daehee Kang, Ji Yeob Choi, Sue K. Park, Dong Young Noh, Jacques Simard, Martine Dumont, Mark S. Goldberg, France Labrèche, Peter A. Fasching, Alexander Hein, Arif B. Ekici, Matthias W. Beckmann, Paolo Radice, Paolo Peterlongo, Jacopo Azzollini, Monica Barile, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, John L. Hopper, Daniel F. Schmidt, Enes Makalic, Melissa C. Southey, Soo Hwang Teo, Cheng Har Yip, Kavitta Sivanandan, Wan Ting Tay, Chen Yang Shen, Chia Ni Hsiung, Jyh Cherng Yu, Ming Feng Hou, Pascal Guénel, Therese Truong, Marie Sanchez, Claire Mulot, William Blot, Qiuyin Cai, Heli Nevanlinna, Taru A. Muranen, Kristiina Aittomäki, Carl Blomqvist, Anna H. Wu, Chiu Chen Tseng, David Van Den Berg, Daniel O. Stram, Natalia Bogdanova, Dörk Thilo Dörk, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Arto Mannermaa, Vesa Kataja, Veli Matti Kosma, Jaana M. Hartikainen, Xiao Ou Shu, Wei Lu, Yu Tang Gao, Ben Zhang, Fergus J. Couch, Amanda E. Toland, Drakoulis Yannoukakos, Suleeporn Sangrajrang, James McKay, Xianshu Wang, Janet E. Olson, Celine Vachon, Kristen Purrington, Gianluca Severi, Laura Baglietto, Christopher A. Haiman, Brian E. Henderson, Fredrick Schumacher, Loic Le Marchand, Peter Devilee, Robert A E M Tollenaar, Caroline Seynaeve, Kamila Czene, Mikael Eriksson, Keith Humphreys, Hatef Darabi, Shahana Ahmed, Mitul Shah, Paul D P Pharoah, Per Hall, Graham G. Giles, Javier Benítez, Alison M. Dunning, Georgia Chenevix-Trench, Douglas F. Easton

Research output: Contribution to journalArticle

Abstract

Candidate variant association studies havebeenlargely unsuccessful in identifyingcommonbreast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data werecombined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR 5 1.07, 95% confidence interval (CI) 5 1.04-1.10, P 5 2.9 3 1026], AKAP9-M463I at 7q21 (rs6964587, OR 5 1.05, 95% CI 5 1.03-1.07, P 5 1.7 3 1026) and NEK10-L513S at 3p24 (rs10510592, OR 5 1.10, 95% CI 5 1.07-1.12, P 5 5.1 3 10217). The first two associations reached genome-wide statistical significance in acombined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR 5 1.07 (95% CI 5 1.05-1.10, P 5 1.0 3 1028); for AKAP9-M463I, OR 5 1.05 (95% CI 5 1.04-1.07, P 5 2.0 3 10210). Further analysis of other common variants in these two regions suggested that intronic SNPsnearby are more strongly associated with disease risk.Wehave thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.

Original languageEnglish (US)
Pages (from-to)6096-6111
Number of pages16
JournalHuman Molecular Genetics
Volume23
Issue number22
DOIs
StatePublished - Nov 15 2014
Externally publishedYes

Fingerprint

Single Nucleotide Polymorphism
Confidence Intervals
Breast Neoplasms
Genome-Wide Association Study
Logistic Models
Alleles
Genome
Genes
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Milne, R. L., Burwinkel, B., Michailidou, K., Arias Perez, J. I., Pilar Zamora, M., Menéndez-Rodríguez, P., ... Easton, D. F. (2014). Common non-synonymous SNPs associated with breast cancer susceptibility: Findings from the Breast Cancer Association Consortium. Human Molecular Genetics, 23(22), 6096-6111. https://doi.org/10.1093/hmg/ddu311

Common non-synonymous SNPs associated with breast cancer susceptibility : Findings from the Breast Cancer Association Consortium. / Milne, Roger L.; Burwinkel, Barbara; Michailidou, Kyriaki; Arias Perez, Jose Ignacio; Pilar Zamora, M.; Menéndez-Rodríguez, Primitiva; Hardisson, David; Mendiola, Marta; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.; Dennis, Joe; Wang, Qin; Bolla, Manjeet K.; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk; Ko, Yon Dschun; Brauch, Hiltrud; Hamann, Ute; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Li, Jingmei; Brand, Judith S.; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lambrechts, Diether; Peuteman, Gilian; Christiaens, Marie Rose; Smeets, Ann; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katazyna; Hartman, Mikael; Hui, Miao; Lim, Wei Yen; Chan, Ching Wan; Marme, Federick; Yang, Rongxi; Bugert, Peter; Lindblom, Annika; Margolin, Sara; García-Closas, Montserrat; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Hooning, Maartje J.; Kriege, Mieke; van den Ouweland, Ans M W; Koppert, Linetta B.; Fletcher, Olivia; Johnson, Nichola; dos-Santos-Silva, Isabel; Peto, Julian; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Cox, Angela; Cross, Simon S.; Reed, Malcolm W R; Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Braaf, Linde; Kang, Daehee; Choi, Ji Yeob; Park, Sue K.; Noh, Dong Young; Simard, Jacques; Dumont, Martine; Goldberg, Mark S.; Labrèche, France; Fasching, Peter A.; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Radice, Paolo; Peterlongo, Paolo; Azzollini, Jacopo; Barile, Monica; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Hopper, John L.; Schmidt, Daniel F.; Makalic, Enes; Southey, Melissa C.; Teo, Soo Hwang; Yip, Cheng Har; Sivanandan, Kavitta; Tay, Wan Ting; Shen, Chen Yang; Hsiung, Chia Ni; Yu, Jyh Cherng; Hou, Ming Feng; Guénel, Pascal; Truong, Therese; Sanchez, Marie; Mulot, Claire; Blot, William; Cai, Qiuyin; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Wu, Anna H.; Tseng, Chiu Chen; Van Den Berg, David; Stram, Daniel O.; Bogdanova, Natalia; Thilo Dörk, Dörk; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Shu, Xiao Ou; Lu, Wei; Gao, Yu Tang; Zhang, Ben; Couch, Fergus J.; Toland, Amanda E.; Yannoukakos, Drakoulis; Sangrajrang, Suleeporn; McKay, James; Wang, Xianshu; Olson, Janet E.; Vachon, Celine; Purrington, Kristen; Severi, Gianluca; Baglietto, Laura; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Marchand, Loic Le; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Ahmed, Shahana; Shah, Mitul; Pharoah, Paul D P; Hall, Per; Giles, Graham G.; Benítez, Javier; Dunning, Alison M.; Chenevix-Trench, Georgia; Easton, Douglas F.

In: Human Molecular Genetics, Vol. 23, No. 22, 15.11.2014, p. 6096-6111.

Research output: Contribution to journalArticle

Milne, RL, Burwinkel, B, Michailidou, K, Arias Perez, JI, Pilar Zamora, M, Menéndez-Rodríguez, P, Hardisson, D, Mendiola, M, González-Neira, A, Pita, G, Rosario Alonso, M, Dennis, J, Wang, Q, Bolla, MK, Swerdlow, A, Ashworth, A, Orr, N, Schoemaker, M, Ko, YD, Brauch, H, Hamann, U, Andrulis, IL, Knight, JA, Glendon, G, Tchatchou, S, Matsuo, K, Ito, H, Iwata, H, Tajima, K, Li, J, Brand, JS, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Lambrechts, D, Peuteman, G, Christiaens, MR, Smeets, A, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Hartman, M, Hui, M, Lim, WY, Chan, CW, Marme, F, Yang, R, Bugert, P, Lindblom, A, Margolin, S, García-Closas, M, Chanock, SJ, Lissowska, J, Figueroa, JD, Bojesen, SE, Nordestgaard, BG, Flyger, H, Hooning, MJ, Kriege, M, van den Ouweland, AMW, Koppert, LB, Fletcher, O, Johnson, N, dos-Santos-Silva, I, Peto, J, Zheng, W, Deming-Halverson, S, Shrubsole, MJ, Long, J, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Cox, A, Cross, SS, Reed, MWR, Schmidt, MK, Broeks, A, Cornelissen, S, Braaf, L, Kang, D, Choi, JY, Park, SK, Noh, DY, Simard, J, Dumont, M, Goldberg, MS, Labrèche, F, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Radice, P, Peterlongo, P, Azzollini, J, Barile, M, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Hopper, JL, Schmidt, DF, Makalic, E, Southey, MC, Teo, SH, Yip, CH, Sivanandan, K, Tay, WT, Shen, CY, Hsiung, CN, Yu, JC, Hou, MF, Guénel, P, Truong, T, Sanchez, M, Mulot, C, Blot, W, Cai, Q, Nevanlinna, H, Muranen, TA, Aittomäki, K, Blomqvist, C, Wu, AH, Tseng, CC, Van Den Berg, D, Stram, DO, Bogdanova, N, Thilo Dörk, D, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, JM, Shu, XO, Lu, W, Gao, YT, Zhang, B, Couch, FJ, Toland, AE, Yannoukakos, D, Sangrajrang, S, McKay, J, Wang, X, Olson, JE, Vachon, C, Purrington, K, Severi, G, Baglietto, L, Haiman, CA, Henderson, BE, Schumacher, F, Marchand, LL, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Czene, K, Eriksson, M, Humphreys, K, Darabi, H, Ahmed, S, Shah, M, Pharoah, PDP, Hall, P, Giles, GG, Benítez, J, Dunning, AM, Chenevix-Trench, G & Easton, DF 2014, 'Common non-synonymous SNPs associated with breast cancer susceptibility: Findings from the Breast Cancer Association Consortium', Human Molecular Genetics, vol. 23, no. 22, pp. 6096-6111. https://doi.org/10.1093/hmg/ddu311
Milne RL, Burwinkel B, Michailidou K, Arias Perez JI, Pilar Zamora M, Menéndez-Rodríguez P et al. Common non-synonymous SNPs associated with breast cancer susceptibility: Findings from the Breast Cancer Association Consortium. Human Molecular Genetics. 2014 Nov 15;23(22):6096-6111. https://doi.org/10.1093/hmg/ddu311
Milne, Roger L. ; Burwinkel, Barbara ; Michailidou, Kyriaki ; Arias Perez, Jose Ignacio ; Pilar Zamora, M. ; Menéndez-Rodríguez, Primitiva ; Hardisson, David ; Mendiola, Marta ; González-Neira, Anna ; Pita, Guillermo ; Rosario Alonso, M. ; Dennis, Joe ; Wang, Qin ; Bolla, Manjeet K. ; Swerdlow, Anthony ; Ashworth, Alan ; Orr, Nick ; Schoemaker, Minouk ; Ko, Yon Dschun ; Brauch, Hiltrud ; Hamann, Ute ; Andrulis, Irene L. ; Knight, Julia A. ; Glendon, Gord ; Tchatchou, Sandrine ; Matsuo, Keitaro ; Ito, Hidemi ; Iwata, Hiroji ; Tajima, Kazuo ; Li, Jingmei ; Brand, Judith S. ; Brenner, Hermann ; Dieffenbach, Aida Karina ; Arndt, Volker ; Stegmaier, Christa ; Lambrechts, Diether ; Peuteman, Gilian ; Christiaens, Marie Rose ; Smeets, Ann ; Jakubowska, Anna ; Lubinski, Jan ; Jaworska-Bieniek, Katarzyna ; Durda, Katazyna ; Hartman, Mikael ; Hui, Miao ; Lim, Wei Yen ; Chan, Ching Wan ; Marme, Federick ; Yang, Rongxi ; Bugert, Peter ; Lindblom, Annika ; Margolin, Sara ; García-Closas, Montserrat ; Chanock, Stephen J. ; Lissowska, Jolanta ; Figueroa, Jonine D. ; Bojesen, Stig E. ; Nordestgaard, Børge G. ; Flyger, Henrik ; Hooning, Maartje J. ; Kriege, Mieke ; van den Ouweland, Ans M W ; Koppert, Linetta B. ; Fletcher, Olivia ; Johnson, Nichola ; dos-Santos-Silva, Isabel ; Peto, Julian ; Zheng, Wei ; Deming-Halverson, Sandra ; Shrubsole, Martha J. ; Long, Jirong ; Chang-Claude, Jenny ; Rudolph, Anja ; Seibold, Petra ; Flesch-Janys, Dieter ; Winqvist, Robert ; Pylkäs, Katri ; Jukkola-Vuorinen, Arja ; Grip, Mervi ; Cox, Angela ; Cross, Simon S. ; Reed, Malcolm W R ; Schmidt, Marjanka K. ; Broeks, Annegien ; Cornelissen, Sten ; Braaf, Linde ; Kang, Daehee ; Choi, Ji Yeob ; Park, Sue K. ; Noh, Dong Young ; Simard, Jacques ; Dumont, Martine ; Goldberg, Mark S. ; Labrèche, France ; Fasching, Peter A. ; Hein, Alexander ; Ekici, Arif B. ; Beckmann, Matthias W. ; Radice, Paolo ; Peterlongo, Paolo ; Azzollini, Jacopo ; Barile, Monica ; Sawyer, Elinor ; Tomlinson, Ian ; Kerin, Michael ; Miller, Nicola ; Hopper, John L. ; Schmidt, Daniel F. ; Makalic, Enes ; Southey, Melissa C. ; Teo, Soo Hwang ; Yip, Cheng Har ; Sivanandan, Kavitta ; Tay, Wan Ting ; Shen, Chen Yang ; Hsiung, Chia Ni ; Yu, Jyh Cherng ; Hou, Ming Feng ; Guénel, Pascal ; Truong, Therese ; Sanchez, Marie ; Mulot, Claire ; Blot, William ; Cai, Qiuyin ; Nevanlinna, Heli ; Muranen, Taru A. ; Aittomäki, Kristiina ; Blomqvist, Carl ; Wu, Anna H. ; Tseng, Chiu Chen ; Van Den Berg, David ; Stram, Daniel O. ; Bogdanova, Natalia ; Thilo Dörk, Dörk ; Muir, Kenneth ; Lophatananon, Artitaya ; Stewart-Brown, Sarah ; Siriwanarangsan, Pornthep ; Mannermaa, Arto ; Kataja, Vesa ; Kosma, Veli Matti ; Hartikainen, Jaana M. ; Shu, Xiao Ou ; Lu, Wei ; Gao, Yu Tang ; Zhang, Ben ; Couch, Fergus J. ; Toland, Amanda E. ; Yannoukakos, Drakoulis ; Sangrajrang, Suleeporn ; McKay, James ; Wang, Xianshu ; Olson, Janet E. ; Vachon, Celine ; Purrington, Kristen ; Severi, Gianluca ; Baglietto, Laura ; Haiman, Christopher A. ; Henderson, Brian E. ; Schumacher, Fredrick ; Marchand, Loic Le ; Devilee, Peter ; Tollenaar, Robert A E M ; Seynaeve, Caroline ; Czene, Kamila ; Eriksson, Mikael ; Humphreys, Keith ; Darabi, Hatef ; Ahmed, Shahana ; Shah, Mitul ; Pharoah, Paul D P ; Hall, Per ; Giles, Graham G. ; Benítez, Javier ; Dunning, Alison M. ; Chenevix-Trench, Georgia ; Easton, Douglas F. / Common non-synonymous SNPs associated with breast cancer susceptibility : Findings from the Breast Cancer Association Consortium. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 22. pp. 6096-6111.
@article{498da89953b54dcc96d028fe41f501f3,
title = "Common non-synonymous SNPs associated with breast cancer susceptibility: Findings from the Breast Cancer Association Consortium",
abstract = "Candidate variant association studies havebeenlargely unsuccessful in identifyingcommonbreast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data werecombined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR 5 1.07, 95{\%} confidence interval (CI) 5 1.04-1.10, P 5 2.9 3 1026], AKAP9-M463I at 7q21 (rs6964587, OR 5 1.05, 95{\%} CI 5 1.03-1.07, P 5 1.7 3 1026) and NEK10-L513S at 3p24 (rs10510592, OR 5 1.10, 95{\%} CI 5 1.07-1.12, P 5 5.1 3 10217). The first two associations reached genome-wide statistical significance in acombined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR 5 1.07 (95{\%} CI 5 1.05-1.10, P 5 1.0 3 1028); for AKAP9-M463I, OR 5 1.05 (95{\%} CI 5 1.04-1.07, P 5 2.0 3 10210). Further analysis of other common variants in these two regions suggested that intronic SNPsnearby are more strongly associated with disease risk.Wehave thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.",
author = "Milne, {Roger L.} and Barbara Burwinkel and Kyriaki Michailidou and {Arias Perez}, {Jose Ignacio} and {Pilar Zamora}, M. and Primitiva Men{\'e}ndez-Rodr{\'i}guez and David Hardisson and Marta Mendiola and Anna Gonz{\'a}lez-Neira and Guillermo Pita and {Rosario Alonso}, M. and Joe Dennis and Qin Wang and Bolla, {Manjeet K.} and Anthony Swerdlow and Alan Ashworth and Nick Orr and Minouk Schoemaker and Ko, {Yon Dschun} and Hiltrud Brauch and Ute Hamann and Andrulis, {Irene L.} and Knight, {Julia A.} and Gord Glendon and Sandrine Tchatchou and Keitaro Matsuo and Hidemi Ito and Hiroji Iwata and Kazuo Tajima and Jingmei Li and Brand, {Judith S.} and Hermann Brenner and Dieffenbach, {Aida Karina} and Volker Arndt and Christa Stegmaier and Diether Lambrechts and Gilian Peuteman and Christiaens, {Marie Rose} and Ann Smeets and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska-Bieniek and Katazyna Durda and Mikael Hartman and Miao Hui and Lim, {Wei Yen} and Chan, {Ching Wan} and Federick Marme and Rongxi Yang and Peter Bugert and Annika Lindblom and Sara Margolin and Montserrat Garc{\'i}a-Closas and Chanock, {Stephen J.} and Jolanta Lissowska and Figueroa, {Jonine D.} and Bojesen, {Stig E.} and Nordestgaard, {B{\o}rge G.} and Henrik Flyger and Hooning, {Maartje J.} and Mieke Kriege and {van den Ouweland}, {Ans M W} and Koppert, {Linetta B.} and Olivia Fletcher and Nichola Johnson and Isabel dos-Santos-Silva and Julian Peto and Wei Zheng and Sandra Deming-Halverson and Shrubsole, {Martha J.} and Jirong Long and Jenny Chang-Claude and Anja Rudolph and Petra Seibold and Dieter Flesch-Janys and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Angela Cox and Cross, {Simon S.} and Reed, {Malcolm W R} and Schmidt, {Marjanka K.} and Annegien Broeks and Sten Cornelissen and Linde Braaf and Daehee Kang and Choi, {Ji Yeob} and Park, {Sue K.} and Noh, {Dong Young} and Jacques Simard and Martine Dumont and Goldberg, {Mark S.} and France Labr{\`e}che and Fasching, {Peter A.} and Alexander Hein and Ekici, {Arif B.} and Beckmann, {Matthias W.} and Paolo Radice and Paolo Peterlongo and Jacopo Azzollini and Monica Barile and Elinor Sawyer and Ian Tomlinson and Michael Kerin and Nicola Miller and Hopper, {John L.} and Schmidt, {Daniel F.} and Enes Makalic and Southey, {Melissa C.} and Teo, {Soo Hwang} and Yip, {Cheng Har} and Kavitta Sivanandan and Tay, {Wan Ting} and Shen, {Chen Yang} and Hsiung, {Chia Ni} and Yu, {Jyh Cherng} and Hou, {Ming Feng} and Pascal Gu{\'e}nel and Therese Truong and Marie Sanchez and Claire Mulot and William Blot and Qiuyin Cai and Heli Nevanlinna and Muranen, {Taru A.} and Kristiina Aittom{\"a}ki and Carl Blomqvist and Wu, {Anna H.} and Tseng, {Chiu Chen} and {Van Den Berg}, David and Stram, {Daniel O.} and Natalia Bogdanova and {Thilo D{\"o}rk}, D{\"o}rk and Kenneth Muir and Artitaya Lophatananon and Sarah Stewart-Brown and Pornthep Siriwanarangsan and Arto Mannermaa and Vesa Kataja and Kosma, {Veli Matti} and Hartikainen, {Jaana M.} and Shu, {Xiao Ou} and Wei Lu and Gao, {Yu Tang} and Ben Zhang and Couch, {Fergus J.} and Toland, {Amanda E.} and Drakoulis Yannoukakos and Suleeporn Sangrajrang and James McKay and Xianshu Wang and Olson, {Janet E.} and Celine Vachon and Kristen Purrington and Gianluca Severi and Laura Baglietto and Haiman, {Christopher A.} and Henderson, {Brian E.} and Fredrick Schumacher and Marchand, {Loic Le} and Peter Devilee and Tollenaar, {Robert A E M} and Caroline Seynaeve and Kamila Czene and Mikael Eriksson and Keith Humphreys and Hatef Darabi and Shahana Ahmed and Mitul Shah and Pharoah, {Paul D P} and Per Hall and Giles, {Graham G.} and Javier Ben{\'i}tez and Dunning, {Alison M.} and Georgia Chenevix-Trench and Easton, {Douglas F.}",
year = "2014",
month = "11",
day = "15",
doi = "10.1093/hmg/ddu311",
language = "English (US)",
volume = "23",
pages = "6096--6111",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "22",

}

TY - JOUR

T1 - Common non-synonymous SNPs associated with breast cancer susceptibility

T2 - Findings from the Breast Cancer Association Consortium

AU - Milne, Roger L.

AU - Burwinkel, Barbara

AU - Michailidou, Kyriaki

AU - Arias Perez, Jose Ignacio

AU - Pilar Zamora, M.

AU - Menéndez-Rodríguez, Primitiva

AU - Hardisson, David

AU - Mendiola, Marta

AU - González-Neira, Anna

AU - Pita, Guillermo

AU - Rosario Alonso, M.

AU - Dennis, Joe

AU - Wang, Qin

AU - Bolla, Manjeet K.

AU - Swerdlow, Anthony

AU - Ashworth, Alan

AU - Orr, Nick

AU - Schoemaker, Minouk

AU - Ko, Yon Dschun

AU - Brauch, Hiltrud

AU - Hamann, Ute

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Glendon, Gord

AU - Tchatchou, Sandrine

AU - Matsuo, Keitaro

AU - Ito, Hidemi

AU - Iwata, Hiroji

AU - Tajima, Kazuo

AU - Li, Jingmei

AU - Brand, Judith S.

AU - Brenner, Hermann

AU - Dieffenbach, Aida Karina

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Lambrechts, Diether

AU - Peuteman, Gilian

AU - Christiaens, Marie Rose

AU - Smeets, Ann

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Jaworska-Bieniek, Katarzyna

AU - Durda, Katazyna

AU - Hartman, Mikael

AU - Hui, Miao

AU - Lim, Wei Yen

AU - Chan, Ching Wan

AU - Marme, Federick

AU - Yang, Rongxi

AU - Bugert, Peter

AU - Lindblom, Annika

AU - Margolin, Sara

AU - García-Closas, Montserrat

AU - Chanock, Stephen J.

AU - Lissowska, Jolanta

AU - Figueroa, Jonine D.

AU - Bojesen, Stig E.

AU - Nordestgaard, Børge G.

AU - Flyger, Henrik

AU - Hooning, Maartje J.

AU - Kriege, Mieke

AU - van den Ouweland, Ans M W

AU - Koppert, Linetta B.

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - dos-Santos-Silva, Isabel

AU - Peto, Julian

AU - Zheng, Wei

AU - Deming-Halverson, Sandra

AU - Shrubsole, Martha J.

AU - Long, Jirong

AU - Chang-Claude, Jenny

AU - Rudolph, Anja

AU - Seibold, Petra

AU - Flesch-Janys, Dieter

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Cox, Angela

AU - Cross, Simon S.

AU - Reed, Malcolm W R

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Cornelissen, Sten

AU - Braaf, Linde

AU - Kang, Daehee

AU - Choi, Ji Yeob

AU - Park, Sue K.

AU - Noh, Dong Young

AU - Simard, Jacques

AU - Dumont, Martine

AU - Goldberg, Mark S.

AU - Labrèche, France

AU - Fasching, Peter A.

AU - Hein, Alexander

AU - Ekici, Arif B.

AU - Beckmann, Matthias W.

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Azzollini, Jacopo

AU - Barile, Monica

AU - Sawyer, Elinor

AU - Tomlinson, Ian

AU - Kerin, Michael

AU - Miller, Nicola

AU - Hopper, John L.

AU - Schmidt, Daniel F.

AU - Makalic, Enes

AU - Southey, Melissa C.

AU - Teo, Soo Hwang

AU - Yip, Cheng Har

AU - Sivanandan, Kavitta

AU - Tay, Wan Ting

AU - Shen, Chen Yang

AU - Hsiung, Chia Ni

AU - Yu, Jyh Cherng

AU - Hou, Ming Feng

AU - Guénel, Pascal

AU - Truong, Therese

AU - Sanchez, Marie

AU - Mulot, Claire

AU - Blot, William

AU - Cai, Qiuyin

AU - Nevanlinna, Heli

AU - Muranen, Taru A.

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Wu, Anna H.

AU - Tseng, Chiu Chen

AU - Van Den Berg, David

AU - Stram, Daniel O.

AU - Bogdanova, Natalia

AU - Thilo Dörk, Dörk

AU - Muir, Kenneth

AU - Lophatananon, Artitaya

AU - Stewart-Brown, Sarah

AU - Siriwanarangsan, Pornthep

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli Matti

AU - Hartikainen, Jaana M.

AU - Shu, Xiao Ou

AU - Lu, Wei

AU - Gao, Yu Tang

AU - Zhang, Ben

AU - Couch, Fergus J.

AU - Toland, Amanda E.

AU - Yannoukakos, Drakoulis

AU - Sangrajrang, Suleeporn

AU - McKay, James

AU - Wang, Xianshu

AU - Olson, Janet E.

AU - Vachon, Celine

AU - Purrington, Kristen

AU - Severi, Gianluca

AU - Baglietto, Laura

AU - Haiman, Christopher A.

AU - Henderson, Brian E.

AU - Schumacher, Fredrick

AU - Marchand, Loic Le

AU - Devilee, Peter

AU - Tollenaar, Robert A E M

AU - Seynaeve, Caroline

AU - Czene, Kamila

AU - Eriksson, Mikael

AU - Humphreys, Keith

AU - Darabi, Hatef

AU - Ahmed, Shahana

AU - Shah, Mitul

AU - Pharoah, Paul D P

AU - Hall, Per

AU - Giles, Graham G.

AU - Benítez, Javier

AU - Dunning, Alison M.

AU - Chenevix-Trench, Georgia

AU - Easton, Douglas F.

PY - 2014/11/15

Y1 - 2014/11/15

N2 - Candidate variant association studies havebeenlargely unsuccessful in identifyingcommonbreast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data werecombined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR 5 1.07, 95% confidence interval (CI) 5 1.04-1.10, P 5 2.9 3 1026], AKAP9-M463I at 7q21 (rs6964587, OR 5 1.05, 95% CI 5 1.03-1.07, P 5 1.7 3 1026) and NEK10-L513S at 3p24 (rs10510592, OR 5 1.10, 95% CI 5 1.07-1.12, P 5 5.1 3 10217). The first two associations reached genome-wide statistical significance in acombined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR 5 1.07 (95% CI 5 1.05-1.10, P 5 1.0 3 1028); for AKAP9-M463I, OR 5 1.05 (95% CI 5 1.04-1.07, P 5 2.0 3 10210). Further analysis of other common variants in these two regions suggested that intronic SNPsnearby are more strongly associated with disease risk.Wehave thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.

AB - Candidate variant association studies havebeenlargely unsuccessful in identifyingcommonbreast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data werecombined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR 5 1.07, 95% confidence interval (CI) 5 1.04-1.10, P 5 2.9 3 1026], AKAP9-M463I at 7q21 (rs6964587, OR 5 1.05, 95% CI 5 1.03-1.07, P 5 1.7 3 1026) and NEK10-L513S at 3p24 (rs10510592, OR 5 1.10, 95% CI 5 1.07-1.12, P 5 5.1 3 10217). The first two associations reached genome-wide statistical significance in acombined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR 5 1.07 (95% CI 5 1.05-1.10, P 5 1.0 3 1028); for AKAP9-M463I, OR 5 1.05 (95% CI 5 1.04-1.07, P 5 2.0 3 10210). Further analysis of other common variants in these two regions suggested that intronic SNPsnearby are more strongly associated with disease risk.Wehave thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.

UR - http://www.scopus.com/inward/record.url?scp=84959227849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959227849&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddu311

DO - 10.1093/hmg/ddu311

M3 - Article

VL - 23

SP - 6096

EP - 6111

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 22

ER -