Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for g1/48% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in g1/470,000 cases and ĝ̂1/468,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 - 10 g 35), 12q24 (rs1292011; P = 4.3 - 10 g 19) and 21q21 (rs2823093; P = 1.1 - 10 g 12). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

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Journal Nature Genetics
Ghoussaini, M, Fletcher, O, Michailidou, K, Turnbull, C, Schmidt, M.K, Dicks, E, … Easton, D.F. (2012). Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nature Genetics, 44(3), 312–318. doi:10.1038/ng.1049