Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

Journal article

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.

Authors: Garcia-Closas, M; Couch, F; Lindstrom, S; Michailidou, K; Schmidt, M

• Publication status: Published
• Journal: Nature genetics
• Volume: 45
• Issue: 4
• Pages: 392-398e2
• Publication date: 2013-04-01
• DOI: 10.1038/ng.2561
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Genetic Loci; kConFab Investigators; Polymorphism, Single Nucleotide; Receptors, Estrogen; Familial Breast Cancer Study (FBCS); Cooperative Behavior; Genetic Predisposition to Disease; Oligonucleotide Array Sequence Analysis; Gene ENvironmental Interaction and breast CAncer (GENICA) Network; Meta-Analysis as Topic; Risk Factors; Case-Control Studies; Australian Breast Cancer Tissue Bank (ABCTB) Investigators; Genome-Wide Association Study; Female; Humans; Genotype; Breast Neoplasms