Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

R L Milne; B Burwinkel; K Michailidou; J I Arias-Perez; M P Zamora; P Menendez-Rodriguez; D Hardisson; M Mendiola; A Gonzalez-Neira; G Pita; M R Alonso; J Dennis; Q Wang; M K Bolla; A Swerdlow; A Ashworth; N Orr; M Schoemaker; Y D Ko; H Brauch; U Hamann; I L Andrulis; J A Knight; G Glendon; S Tchatchou; K Investigators; K Matsuo; H Ito; H Iwata; K Tajima; J Li; J S Brand; H Brenner; A K Dieffenbach; V Arndt; C Stegmaier; D Lambrechts; G Peuteman; M R Christiaens; A Smeets; A Jakubowska; J Lubinski; K Jaworska-Bieniek; K Durda; M Hartman; M Hui; W Y Lim; C W Chan; F Marme; R Yang; P Bugert; A Lindblom; S Margolin; M Garcia-Closas; S J Chanock; J Lissowska; J D Figueroa; S E Bojesen; B G Nordestgaard; H Flyger; M J Hooning; M Kriege; A M van den Ouweland; L B Koppert; O Fletcher; N Johnson; I Dos-Santos-Silva; J Peto; W Zheng; S Deming-Halverson; M J Shrubsole; J Long; J Chang-Claude; A Rudolph; P Seibold; D Flesch-Janys; R Winqvist; K Pylkas; A Jukkola-Vuorinen; M Grip; A Cox; S S Cross; M W Reed; M K Schmidt; A Broeks; S Cornelissen; L Braaf; D Kang; J Y Choi; S K Park; D Y Noh; J Simard; M Dumont; M S Goldberg; F Labreche; P A Fasching; A Hein; A B Ekici; M W Beckmann; P Radice; P Peterlongo; J Azzollini; M Barile; E Sawyer; I Tomlinson; M Kerin; N Miller; J L Hopper; D F Schmidt; E Makalic; M C Southey; S H Teo; C H Yip; K Sivanandan; W T Tay; C Y Shen; C N Hsiung; J C Yu; M F Hou; P Guenel; T Truong; M Sanchez; C Mulot; W Blot; Q Cai; H Nevanlinna; T A Muranen; K Aittomaki; C Blomqvist; A H Wu; C C Tseng; D Van Den Berg; D O Stram; N Bogdanova; T Dork; K Muir; A Lophatananon; S Stewart-Brown; P Siriwanarangsan; A Mannermaa; V Kataja; V M Kosma; J M Hartikainen; X O Shu; W Lu; Y T Gao; B Zhang; F J Couch; A E Toland; D Yannoukakos; S Sangrajrang; J McKay; X Wang; J E Olson; C Vachon; K Purrington; G Severi; L Baglietto; C A Haiman; B E Henderson; F Schumacher; L Le Marchand; P Devilee; R A Tollenaar; C Seynaeve; K Czene; M Eriksson; K Humphreys; H Darabi; S Ahmed; M Shah; P D Pharoah; P Hall; G G Giles; J Benitez; A M Dunning; G Chenevix-Trench; D F Easton

doi:10.1093/hmg/ddu311

Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

R L Milne, B Burwinkel, K Michailidou, J I Arias-Perez, M P Zamora, P Menendez-Rodriguez, D Hardisson, M Mendiola, A Gonzalez-Neira, G Pita, M R Alonso, J Dennis, Q Wang, M K Bolla, A Swerdlow, A Ashworth, N Orr, M Schoemaker, Y D Ko, H BrauchU Hamann, I L Andrulis, J A Knight, G Glendon, S Tchatchou, K Investigators, K Matsuo, H Ito, H Iwata, K Tajima, J Li, J S Brand, H Brenner, A K Dieffenbach, V Arndt, C Stegmaier, D Lambrechts, G Peuteman, M R Christiaens, A Smeets, A Jakubowska, J Lubinski, K Jaworska-Bieniek, K Durda, M Hartman, M Hui, W Y Lim, C W Chan, F Marme, R Yang, P Bugert, A Lindblom, S Margolin, M Garcia-Closas, S J Chanock, J Lissowska, J D Figueroa, S E Bojesen, B G Nordestgaard, H Flyger, M J Hooning, M Kriege, A M van den Ouweland, L B Koppert, O Fletcher, N Johnson, I Dos-Santos-Silva, J Peto, W Zheng, S Deming-Halverson, M J Shrubsole, J Long, J Chang-Claude, A Rudolph, P Seibold, D Flesch-Janys, R Winqvist, K Pylkas, A Jukkola-Vuorinen, M Grip, A Cox, S S Cross, M W Reed, M K Schmidt, A Broeks, S Cornelissen, L Braaf, D Kang, J Y Choi, S K Park, D Y Noh, J Simard, M Dumont, M S Goldberg, F Labreche, P A Fasching, A Hein, A B Ekici, M W Beckmann, P Radice, P Peterlongo, J Azzollini, M Barile, E Sawyer, I Tomlinson, M Kerin, N Miller, J L Hopper, D F Schmidt, E Makalic, M C Southey, S H Teo, C H Yip, K Sivanandan, W T Tay, C Y Shen, C N Hsiung, J C Yu, M F Hou, P Guenel, T Truong, M Sanchez, C Mulot, W Blot, Q Cai, H Nevanlinna, T A Muranen, K Aittomaki, C Blomqvist, A H Wu, C C Tseng, D Van Den Berg, D O Stram, N Bogdanova, T Dork, K Muir, A Lophatananon, S Stewart-Brown, P Siriwanarangsan, A Mannermaa, V Kataja, V M Kosma, J M Hartikainen, X O Shu, W Lu, Y T Gao, B Zhang, F J Couch, A E Toland, D Yannoukakos, S Sangrajrang, J McKay, X Wang, J E Olson, C Vachon, K Purrington, G Severi, L Baglietto, C A Haiman, B E Henderson, F Schumacher, L Le Marchand, P Devilee, R A Tollenaar, C Seynaeve, K Czene, M Eriksson, K Humphreys, H Darabi, S Ahmed, M Shah, P D Pharoah, P Hall, G G Giles, J Benitez, A M Dunning, G Chenevix-Trench, D F Easton

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

Abstract

Candidate variant association studies have been largely unsuccessful in identifying common breast 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 were combined from 38 studies of white European women (46,450 cases and 42,600 controls) and analysed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 (rs1053338, per-allele OR=1.07, 95%CI=1.04-1.10, P=2.9x10-6), AKAP9-M463I at 7q21 (rs6964587, OR=1.05, 95%CI=1.03-1.07, P=1.7x10-6) and NEK10-L513S at 3p24 (rs10510592, OR=1.10, 95%CI=1.07-1.12, P=5.1x10-17). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine GWAS: for ATXN7-K264R, OR=1.07 (95%CI=1.05-1.10, P=1.0x10-8); for AKAP9-M463I, OR=1.05 (95%CI=1.04-1.07, P=2.0x10-10). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have 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 genome-wide association study (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 language	English
Journal	Hum Mol Genet
DOIs	https://doi.org/10.1093/hmg/ddu311
Publication status	Published - 2014

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/hmg/ddu311

Cite this

Milne, R. L., Burwinkel, B., Michailidou, K., Arias-Perez, J. I., Zamora, M. P., Menendez-Rodriguez, P., Hardisson, D., Mendiola, M., Gonzalez-Neira, A., Pita, G., Alonso, M. R., Dennis, J., Wang, Q., Bolla, M. K., Swerdlow, A., Ashworth, A., Orr, N., Schoemaker, M., Ko, Y. D., ... Easton, D. F. (2014). Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium. Hum Mol Genet. https://doi.org/10.1093/hmg/ddu311

@article{b373ae49a843480e8c154b125d5bd60e,

title = "Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium",

abstract = "Candidate variant association studies have been largely unsuccessful in identifying common breast 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 were combined from 38 studies of white European women (46,450 cases and 42,600 controls) and analysed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 (rs1053338, per-allele OR=1.07, 95%CI=1.04-1.10, P=2.9x10-6), AKAP9-M463I at 7q21 (rs6964587, OR=1.05, 95%CI=1.03-1.07, P=1.7x10-6) and NEK10-L513S at 3p24 (rs10510592, OR=1.10, 95%CI=1.07-1.12, P=5.1x10-17). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine GWAS: for ATXN7-K264R, OR=1.07 (95%CI=1.05-1.10, P=1.0x10-8); for AKAP9-M463I, OR=1.05 (95%CI=1.04-1.07, P=2.0x10-10). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have 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 genome-wide association study (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, {R L} and B Burwinkel and K Michailidou and Arias-Perez, {J I} and Zamora, {M P} and P Menendez-Rodriguez and D Hardisson and M Mendiola and A Gonzalez-Neira and G Pita and Alonso, {M R} and J Dennis and Q Wang and Bolla, {M K} and A Swerdlow and A Ashworth and N Orr and M Schoemaker and Ko, {Y D} and H Brauch and U Hamann and Andrulis, {I L} and Knight, {J A} and G Glendon and S Tchatchou and K Investigators and K Matsuo and H Ito and H Iwata and K Tajima and J Li and Brand, {J S} and H Brenner and Dieffenbach, {A K} and V Arndt and C Stegmaier and D Lambrechts and G Peuteman and Christiaens, {M R} and A Smeets and A Jakubowska and J Lubinski and K Jaworska-Bieniek and K Durda and M Hartman and M Hui and Lim, {W Y} and Chan, {C W} and F Marme and R Yang and P Bugert and A Lindblom and S Margolin and M Garcia-Closas and Chanock, {S J} and J Lissowska and Figueroa, {J D} and Bojesen, {S E} and Nordestgaard, {B G} and H Flyger and Hooning, {M J} and M Kriege and {van den Ouweland}, {A M} and Koppert, {L B} and O Fletcher and N Johnson and I Dos-Santos-Silva and J Peto and W Zheng and S Deming-Halverson and Shrubsole, {M J} and J Long and J Chang-Claude and A Rudolph and P Seibold and D Flesch-Janys and R Winqvist and K Pylkas and A Jukkola-Vuorinen and M Grip and A Cox and Cross, {S S} and Reed, {M W} and Schmidt, {M K} and A Broeks and S Cornelissen and L Braaf and D Kang and Choi, {J Y} and Park, {S K} and Noh, {D Y} and J Simard and M Dumont and Goldberg, {M S} and F Labreche and Fasching, {P A} and A Hein and Ekici, {A B} and Beckmann, {M W} and P Radice and P Peterlongo and J Azzollini and M Barile and E Sawyer and I Tomlinson and M Kerin and N Miller and Hopper, {J L} and Schmidt, {D F} and E Makalic and Southey, {M C} and Teo, {S H} and Yip, {C H} and K Sivanandan and Tay, {W T} and Shen, {C Y} and Hsiung, {C N} and Yu, {J C} and Hou, {M F} and P Guenel and T Truong and M Sanchez and C Mulot and W Blot and Q Cai and H Nevanlinna and Muranen, {T A} and K Aittomaki and C Blomqvist and Wu, {A H} and Tseng, {C C} and {Van Den Berg}, D and Stram, {D O} and N Bogdanova and T Dork and K Muir and A Lophatananon and S Stewart-Brown and P Siriwanarangsan and A Mannermaa and V Kataja and Kosma, {V M} and Hartikainen, {J M} and Shu, {X O} and W Lu and Gao, {Y T} and B Zhang and Couch, {F J} and Toland, {A E} and D Yannoukakos and S Sangrajrang and J McKay and X Wang and Olson, {J E} and C Vachon and K Purrington and G Severi and L Baglietto and Haiman, {C A} and Henderson, {B E} and F Schumacher and {Le Marchand}, L and P Devilee and Tollenaar, {R A} and C Seynaeve and K Czene and M Eriksson and K Humphreys and H Darabi and S Ahmed and M Shah and Pharoah, {P D} and P Hall and Giles, {G G} and J Benitez and Dunning, {A M} and G Chenevix-Trench and Easton, {D F}",

note = "Milne, Roger L Burwinkel, Barbara Michailidou, Kyriaki Arias-Perez, Jose-Ignacio Zamora, M Pilar Menendez-Rodriguez, Primitiva Hardisson, David Mendiola, Marta Gonzalez-Neira, Anna Pita, Guillermo Alonso, M Rosario Dennis, Joe Wang, Qin Bolla, Manjeet K Swerdlow, Anthony Ashworth, Alan Orr, Nick Schoemaker, Minouk Ko, Yon-Dschun Brauch, Hiltrud Hamann, Ute The GENICA Network Andrulis, Irene L Knight, Julia A Glendon, Gord Tchatchou, Sandrine Investigators, kConFab Australian Ovarian Cancer Study Group 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 Garcia-Closas, Montserrat Chanock, Stephen J Lissowska, Jolanta Figueroa, Jonine D Bojesen, Stig E Nordestgaard, Borge 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 Pylkas, 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 Labreche, 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 Guenel, Pascal Truong, Therese Sanchez, Marie Mulot, Claire Blot, William Cai, Qiuyin Nevanlinna, Heli Muranen, Taru A Aittomaki, Kristiina Blomqvist, Carl Wu, Anna H Tseng, Chiu-Chen Van Den Berg, David Stram, Daniel O Bogdanova, Natalia Dork, Thilo 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 Tnbcc 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 Le Marchand, Loic 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 Benitez, Javier Dunning, Alison M Chenevix-Trench, Georgia Easton, Douglas F Human molecular genetics Hum Mol Genet. 2014 Jun 18. pii: ddu311.",

year = "2014",

doi = "10.1093/hmg/ddu311",

language = "English",

journal = "Hum Mol Genet",

issn = "0964-6906",

publisher = "Oxford University Press",

}

Milne, RL, Burwinkel, B, Michailidou, K, Arias-Perez, JI, Zamora, MP, Menendez-Rodriguez, P, Hardisson, D, Mendiola, M, Gonzalez-Neira, A, Pita, G, Alonso, MR, 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, Investigators, K, 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, Garcia-Closas, M, Chanock, SJ, Lissowska, J, Figueroa, JD, Bojesen, SE, Nordestgaard, BG, Flyger, H, Hooning, MJ, Kriege, M, van den Ouweland, AM, 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, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Cox, A, Cross, SS, Reed, MW, Schmidt, MK, Broeks, A, Cornelissen, S, Braaf, L, Kang, D, Choi, JY, Park, SK, Noh, DY, Simard, J, Dumont, M, Goldberg, MS, Labreche, 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, Guenel, P, Truong, T, Sanchez, M, Mulot, C, Blot, W, Cai, Q, Nevanlinna, H, Muranen, TA, Aittomaki, K, Blomqvist, C, Wu, AH, Tseng, CC, Van Den Berg, D, Stram, DO, Bogdanova, N, Dork, T, 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, Le Marchand, L, Devilee, P, Tollenaar, RA, Seynaeve, C, Czene, K, Eriksson, M, Humphreys, K, Darabi, H, Ahmed, S, Shah, M, Pharoah, PD, Hall, P, Giles, GG, Benitez, 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', Hum Mol Genet. https://doi.org/10.1093/hmg/ddu311

TY - JOUR

T1 - Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

AU - Milne, R L

AU - Burwinkel, B

AU - Michailidou, K

AU - Arias-Perez, J I

AU - Zamora, M P

AU - Menendez-Rodriguez, P

AU - Hardisson, D

AU - Mendiola, M

AU - Gonzalez-Neira, A

AU - Pita, G

AU - Alonso, M R

AU - Dennis, J

AU - Wang, Q

AU - Bolla, M K

AU - Swerdlow, A

AU - Ashworth, A

AU - Orr, N

AU - Schoemaker, M

AU - Ko, Y D

AU - Brauch, H

AU - Hamann, U

AU - Andrulis, I L

AU - Knight, J A

AU - Glendon, G

AU - Tchatchou, S

AU - Investigators, K

AU - Matsuo, K

AU - Ito, H

AU - Iwata, H

AU - Tajima, K

AU - Li, J

AU - Brand, J S

AU - Brenner, H

AU - Dieffenbach, A K

AU - Arndt, V

AU - Stegmaier, C

AU - Lambrechts, D

AU - Peuteman, G

AU - Christiaens, M R

AU - Smeets, A

AU - Jakubowska, A

AU - Lubinski, J

AU - Jaworska-Bieniek, K

AU - Durda, K

AU - Hartman, M

AU - Hui, M

AU - Lim, W Y

AU - Chan, C W

AU - Marme, F

AU - Yang, R

AU - Bugert, P

AU - Lindblom, A

AU - Margolin, S

AU - Garcia-Closas, M

AU - Chanock, S J

AU - Lissowska, J

AU - Figueroa, J D

AU - Bojesen, S E

AU - Nordestgaard, B G

AU - Flyger, H

AU - Hooning, M J

AU - Kriege, M

AU - van den Ouweland, A M

AU - Koppert, L B

AU - Fletcher, O

AU - Johnson, N

AU - Dos-Santos-Silva, I

AU - Peto, J

AU - Zheng, W

AU - Deming-Halverson, S

AU - Shrubsole, M J

AU - Long, J

AU - Chang-Claude, J

AU - Rudolph, A

AU - Seibold, P

AU - Flesch-Janys, D

AU - Winqvist, R

AU - Pylkas, K

AU - Jukkola-Vuorinen, A

AU - Grip, M

AU - Cox, A

AU - Cross, S S

AU - Reed, M W

AU - Schmidt, M K

AU - Broeks, A

AU - Cornelissen, S

AU - Braaf, L

AU - Kang, D

AU - Choi, J Y

AU - Park, S K

AU - Noh, D Y

AU - Simard, J

AU - Dumont, M

AU - Goldberg, M S

AU - Labreche, F

AU - Fasching, P A

AU - Hein, A

AU - Ekici, A B

AU - Beckmann, M W

AU - Radice, P

AU - Peterlongo, P

AU - Azzollini, J

AU - Barile, M

AU - Sawyer, E

AU - Tomlinson, I

AU - Kerin, M

AU - Miller, N

AU - Hopper, J L

AU - Schmidt, D F

AU - Makalic, E

AU - Southey, M C

AU - Teo, S H

AU - Yip, C H

AU - Sivanandan, K

AU - Tay, W T

AU - Shen, C Y

AU - Hsiung, C N

AU - Yu, J C

AU - Hou, M F

AU - Guenel, P

AU - Truong, T

AU - Sanchez, M

AU - Mulot, C

AU - Blot, W

AU - Cai, Q

AU - Nevanlinna, H

AU - Muranen, T A

AU - Aittomaki, K

AU - Blomqvist, C

AU - Wu, A H

AU - Tseng, C C

AU - Van Den Berg, D

AU - Stram, D O

AU - Bogdanova, N

AU - Dork, T

AU - Muir, K

AU - Lophatananon, A

AU - Stewart-Brown, S

AU - Siriwanarangsan, P

AU - Mannermaa, A

AU - Kataja, V

AU - Kosma, V M

AU - Hartikainen, J M

AU - Shu, X O

AU - Lu, W

AU - Gao, Y T

AU - Zhang, B

AU - Couch, F J

AU - Toland, A E

AU - Yannoukakos, D

AU - Sangrajrang, S

AU - McKay, J

AU - Wang, X

AU - Olson, J E

AU - Vachon, C

AU - Purrington, K

AU - Severi, G

AU - Baglietto, L

AU - Haiman, C A

AU - Henderson, B E

AU - Schumacher, F

AU - Le Marchand, L

AU - Devilee, P

AU - Tollenaar, R A

AU - Seynaeve, C

AU - Czene, K

AU - Eriksson, M

AU - Humphreys, K

AU - Darabi, H

AU - Ahmed, S

AU - Shah, M

AU - Pharoah, P D

AU - Hall, P

AU - Giles, G G

AU - Benitez, J

AU - Dunning, A M

AU - Chenevix-Trench, G

AU - Easton, D F

N1 - Milne, Roger L Burwinkel, Barbara Michailidou, Kyriaki Arias-Perez, Jose-Ignacio Zamora, M Pilar Menendez-Rodriguez, Primitiva Hardisson, David Mendiola, Marta Gonzalez-Neira, Anna Pita, Guillermo Alonso, M Rosario Dennis, Joe Wang, Qin Bolla, Manjeet K Swerdlow, Anthony Ashworth, Alan Orr, Nick Schoemaker, Minouk Ko, Yon-Dschun Brauch, Hiltrud Hamann, Ute The GENICA Network Andrulis, Irene L Knight, Julia A Glendon, Gord Tchatchou, Sandrine Investigators, kConFab Australian Ovarian Cancer Study Group 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 Garcia-Closas, Montserrat Chanock, Stephen J Lissowska, Jolanta Figueroa, Jonine D Bojesen, Stig E Nordestgaard, Borge 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 Pylkas, 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 Labreche, 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 Guenel, Pascal Truong, Therese Sanchez, Marie Mulot, Claire Blot, William Cai, Qiuyin Nevanlinna, Heli Muranen, Taru A Aittomaki, Kristiina Blomqvist, Carl Wu, Anna H Tseng, Chiu-Chen Van Den Berg, David Stram, Daniel O Bogdanova, Natalia Dork, Thilo 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 Tnbcc 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 Le Marchand, Loic 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 Benitez, Javier Dunning, Alison M Chenevix-Trench, Georgia Easton, Douglas F Human molecular genetics Hum Mol Genet. 2014 Jun 18. pii: ddu311.

PY - 2014

Y1 - 2014

N2 - Candidate variant association studies have been largely unsuccessful in identifying common breast 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 were combined from 38 studies of white European women (46,450 cases and 42,600 controls) and analysed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 (rs1053338, per-allele OR=1.07, 95%CI=1.04-1.10, P=2.9x10-6), AKAP9-M463I at 7q21 (rs6964587, OR=1.05, 95%CI=1.03-1.07, P=1.7x10-6) and NEK10-L513S at 3p24 (rs10510592, OR=1.10, 95%CI=1.07-1.12, P=5.1x10-17). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine GWAS: for ATXN7-K264R, OR=1.07 (95%CI=1.05-1.10, P=1.0x10-8); for AKAP9-M463I, OR=1.05 (95%CI=1.04-1.07, P=2.0x10-10). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have 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 genome-wide association study (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 have been largely unsuccessful in identifying common breast 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 were combined from 38 studies of white European women (46,450 cases and 42,600 controls) and analysed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 (rs1053338, per-allele OR=1.07, 95%CI=1.04-1.10, P=2.9x10-6), AKAP9-M463I at 7q21 (rs6964587, OR=1.05, 95%CI=1.03-1.07, P=1.7x10-6) and NEK10-L513S at 3p24 (rs10510592, OR=1.10, 95%CI=1.07-1.12, P=5.1x10-17). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine GWAS: for ATXN7-K264R, OR=1.07 (95%CI=1.05-1.10, P=1.0x10-8); for AKAP9-M463I, OR=1.05 (95%CI=1.04-1.07, P=2.0x10-10). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have 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 genome-wide association study (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.

U2 - 10.1093/hmg/ddu311

DO - 10.1093/hmg/ddu311

M3 - Article

SN - 0964-6906

JO - Hum Mol Genet

JF - Hum Mol Genet

ER -

Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this