Title: Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.
Authors: Milne, Roger L (see original citation for additional authors)
Published In Nat Genet, (2017 Dec)
Abstract: Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
PubMed ID: 29058716
MeSH Terms: BRCA1 Protein/genetics*; Breast Neoplasms/ethnology; Breast Neoplasms/genetics*; Breast Neoplasms/metabolism; European Continental Ancestry Group/genetics; Female; Genetic Predisposition to Disease/ethnology; Genetic Predisposition to Disease/genetics*; Genome-Wide Association Study/methods; Heterozygote; Humans; Mutation*; Polymorphism, Single Nucleotide*; Receptors, Estrogen/metabolism; Risk Factors