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- Title
Genome-wide association studies identify four ER negative-specific breast cancer risk loci.
- Authors
Garcia-Closas, Montserrat; Feigelson, Heather S; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cross, Simon S; Le Marchand, Loic; Cai, Qiuyin; Shah, Mitul; Dunning, Alison M; Miao, Hui; Chia, Kee Seng; Chan, Ching Wan; Hsiung, Chia-Ni
- Abstract
Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.
- Subjects
BREAST cancer risk factors; ESTROGEN receptors; GENOMES; TUMOR genetics; ETIOLOGY of diseases; SINGLE nucleotide polymorphisms
- Publication
Nature Genetics, 2013, Vol 45, Issue 4, p392
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.2561