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

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Ghoussaini, Maya ; Fletcher, Olivia ; Michailidou, Kyriaki ; Turnbull, Clare ; Schmidt, Marjanka K ; Dicks, Ed ; Dennis, Joe ; Wang, Qin ; Humphreys, Manjeet K ; Luccarini, Craig ; Baynes, Caroline ; Conroy, Don ; Maranian, Melanie ; Ahmed, Shahana ; Driver, Kristy ; Johnson, Nichola ; Orr, Nicholas ; Silva, Isabel dos Santos ; Waisfisz, Quinten ; Meijers-Heijboer, Hanne ; Uitterlinden, Andre G. ; Rivadeneira, Fernando ; Hall, Per ; Czene, Kamila ; Irwanto, Astrid ; Liu, Jianjun ; Nevanlinna, Heli ; Aittomäki, Kristiina ; Blomqvist, Carl ; Meindl, Alfons ... view all 182 authors (2013)
  • Publisher: Nature Publishing Group
  • Journal: volume 44, issue 3, pages 312-318 (issn: 1061-4036, eissn: 1546-1718)
  • Related identifiers: doi: 10.1038/ng.1049, pmc: PMC3653403
  • Subject: Article

: Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ?8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ?70,000 cases and ?68,000 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(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-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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