Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.
Nature genetics 2014 ; 47: 373-80.
Michailidou K, Beesley J, Lindström S, Canisius S, Dennis J, Lush MJ, Maranian MJ, Bolla MK, Wang Q, Shah M, Perkins BJ, Czene K, Eriksson M, Darabi H, Brand JS, Bojesen SE, Nordestgaard BG, Flyger H, Nielsen SF, Rahman N, Turnbull C, BOCS BOCS, Fletcher O, Peto J, Gibson L, Dos-Santos-Silva I, Chang-Claude J, Flesch-Janys D, Rudolph A, Eilber U, Behrens S, Nevanlinna H, Muranen TA, Aittomäki K, Blomqvist C, Khan S, Aaltonen K, Ahsan H, Kibriya MG, Whittemore AS, John EM, Malone KE, Gammon MD, Santella RM, Ursin G, Makalic E, Schmidt DF, Casey G, Hunter DJ, Gapstur SM, Gaudet MM, Diver WR, Haiman CA, Schumacher F, Henderson BE, Le Marchand L, Berg CD, Chanock SJ, Figueroa J, Hoover RN, Lambrechts D, Neven P, Wildiers H, van Limbergen E, Schmidt MK, Broeks A, Verhoef S, Cornelissen S, Couch FJ, Olson JE, Hallberg E, Vachon C, Waisfisz Q, Meijers-Heijboer H, Adank MA, Van Der Luijt RB, Li J, Liu J, Humphreys K, Kang D, Choi JY, Park SK, Yoo KY, Matsuo K, Ito H, Iwata H, Tajima K, Guénel P, Truong T, Mulot C, Sánchez M, Burwinkel B, Marme F, Surowy H, Sohn C, Wu AH, Tseng CC, Van Den Berg D, Stram DO, González-Neira A, Benitez J, Zamora MP, Perez JI, Shu XO, Lu W, Gao YT, Cai H, Cox A, Cross SS, Reed MW, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, kConFab Investigators kConFab Investigators, AOCS Group AOCS Group, Lindblom A, Margolin S, Teo SH, Yip CH, Taib NA, Tan GH, Hooning MJ, Hollestelle A, Martens JW, Collée JM, Blot W, Signorello LB, Cai Q, Hopper JL, Southey MC, Tsimiklis H, Apicella C, Shen CY, Hsiung CN, Wu PE, Hou MF, Kristensen VN, Nord S, Alnaes GI, NBCS NBCS, Giles GG, Milne RL, McLean C, Canzian F, Trichopoulos D, Peeters P, Lund E, Sund M, Khaw KT, Gunter MJ, Palli D, Mortensen LM, Dossus L, Huerta JM, Meindl A, Schmutzler RK, Sutter C, Yang R, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Hartman M, Miao H, Chia KS, Chan CW, Fasching PA, Hein A, Beckmann MW, Haeberle L, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Ashworth A, Orr N, Schoemaker MJ, Swerdlow AJ, Brinton L, García-Closas M, Zheng W, Halverson SL, Shrubsole M, Long J, Goldberg MS, Labrèche F, Dumont M, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Brauch H, Hamann U, Brüning T, GENICA Network GENICA Network, Radice P, Peterlongo P, Manoukian S, Bernard L, Bogdanova NV, Dörk T, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Devilee P, Tollenaar RA, Seynaeve C, van Asperen CJ, Jakubowska A, Lubinski J, Jaworska K, Huzarski T, Sangrajrang S, Gaborieau V, Brennan P, McKay J, Slager S, Toland AE, Ambrosone CB, Yannoukakos D, Kabisch M, Torres D, Neuhausen SL, Anton-Culver H, Luccarini C, Baynes C, Ahmed S, Healey CS, Tessier DC, Vincent D, Bacot F, Pita G, Alonso MR, Álvarez N, Herrero D, Simard J, Pharoah PP, Kraft P, Dunning AM, Chenevix-Trench G, Hall P, Easton DF
DOI : NIHMS664248
PubMed ID : 25751625
PMCID : PMC4549775
URL : https://dx.doi.org/NIHMS664248
Abstract
Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.