title: Genome-wide association studies identify four ER negative-specific breast cancer risk loci.
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.
authors.affiliation: 1] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK. [2] Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK. [3].
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mesh_terms: D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003299:Cooperative Behavior; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015201:Meta-Analysis as Topic; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D011960:Receptors, Estrogen
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