Journal
NATURE GENETICS
Volume 45, Issue 4, Pages 392-398Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2561
Keywords
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Categories
Funding
- Cancer Research UK [C1287/A10118, C1287/Al2014]
- European Community's Seventh Framework Programme [223175, HEALTH-F2-2009-223175]
- European Union European Cooperation in Science and Technology (COST) [BM0606]
- US National Cancer Institute [U01-CA98233, U01-CA98710, U01CA98216, U01-CA98758]
- Intramural Research Program of the US National Institutes of Health (NIH)/National Cancer Institute, Division of Cancer Epidemiology and Genetics
- Mayo Clinic Breast Cancer Study (MCBCS)
- US NIH [CA122340, CA116201]
- Komen Foundation
- European Union [HEALTH-F2-2009223175]
- Breast Cancer Research Foundation
- Canadian Institutes of Health Research (CIHR)
- Ministry of Economic Development, Innovation and Export Trade of Quebec [PSR-SIIRI701]
- US NIH Cancer Post-Cancer GWAS initiative [U19 CA 148065-01]
- Grants-in-Aid for Scientific Research [24590776] Funding Source: KAKEN
- Cancer Foundation Finland sr [110135] Funding Source: researchfish
- Cancer Research UK [15106, 16565, 14136, 16561, 22310, 10118, 11022] Funding Source: researchfish
- Medical Research Council [G1000143, G0401527] Funding Source: researchfish
- National Breast Cancer Foundation [PF-11-20, IF-12-06, IF-12-05] Funding Source: researchfish
- National Institute for Health Research [03/DHCS/03/G121/51] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
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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 metaanalysis 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 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 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.
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