近日，《自然—遗传学》发表的一项研究表明，乳腺癌的易感性与若干遗传变异有关。乳腺癌作为女性常见癌症，每年新增病例可多达100万。
在这项研究中，Douglas Easton与同事对包括全球40多个研究在内的7万个乳腺癌案例以及6.8万个对照案例进行了全基因组关联分析，鉴定出3个与乳腺癌易感性相关的基因区域。其中两个基因区域仅仅与雌激素受体阳性乳腺癌有关联。同时，他们注意到数个可能与乳腺发育和乳腺癌细胞生长相关的基因，或将有助于揭示乳腺癌的发病机制。（生物谷 Bioon.com）
doi:10.1038/ng.1049
PMC:
PMID:
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 Conroy, Melanie Maranian, Shahana Ahmed, Kristy Driver, Nichola Johnson, Nicholas Orr, Isabel dos Santos Silva, Quinten Waisfisz, Hanne Meijers-Heijboer, Andre G Uitterlinden, Fernando Rivadeneira, Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer (HEBON), Per Hall, Kamila C
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.
