Genome-wide association analysis identifies three new breast cancer susceptibility loci

Maya Ghoussaini, Olivia Fletcher, Kyriaki Michailidou, Clare Turnbull, Marjanka K. Schmidt, Ed Dicks, Joe Dennis, Qin Wang, Manjeet K. Humphreys, Craig Luccarini, Caroline Baynes, Don M. Conroy, Melanie J Maranian, Shahana Ahmed, Kristy Driver, Nichola Johnson, Nicholas Orr, Isabel Dos Santos Silva, Quinten Waisfisz, Hanne Meijers-HeijboerMelissa Southey, Graham G. Giles, Catriona McLean

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222 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)312-318
Number of pages7
JournalNature Genetics
Issue number3
Publication statusPublished - Mar 2012
Externally publishedYes

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