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Nat Commun. 2014 Oct 20;5:5260. doi: 10.1038/ncomms6260.

Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25.

Author information

1
Division of General Internal Medicine, Department of Medicine, Institute of Human Genetics, University of California San Fancisco, San Francisco, California 94158, USA.
2
Department of Surgery, University of California San Francisco, San Francisco, California 94122, USA.
3
University of Minnesota Genomics Center, Minneapolis, Minnesota 55455, USA.
4
1] Cancer Prevention Institute of California, Fremont, California 94538, USA [2] Division of Epidemiology, Department of Health Research and Policy, Stanford Cancer Institute, Stanford University School of Medicine, Palo Alto, California 94305, USA.
5
National Institute of Public Health, Cuernavaca 62100, Mexico.
6
1] Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, California 95616, USA [2] Research Group, Citogenética Filogenia y Evolución de Poblaciones, University of Tolima, Ibagué 7652000, Colombia.
7
Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, California 95616, USA.
8
Research Group, Citogenética Filogenia y Evolución de Poblaciones, University of Tolima, Ibagué 7652000, Colombia.
9
Department of Genetics, Stanford University, Palo Alto, California 94305, USA.
10
Division of Pulmonary and Critical Care, Department of Medicine, Institute for Human Genetics, University of California San Francisco, San Francisco, California 94158, USA.
11
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
12
University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA.
13
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
14
Department of Preventive Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
15
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
16
Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

Abstract

The genetic contributions to breast cancer development among Latinas are not well understood. Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 5' of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53-0.67, P=9 × 10(-18)), originates from Indigenous Americans and is uncorrelated with previously reported risk variants at 6q25. The association is stronger for oestrogen receptor-negative disease (OR 0.34, 95% CI 0.21-0.54) than oestrogen receptor-positive disease (OR 0.63, 95% CI 0.49-0.80; P heterogeneity=0.01) and is also associated with mammographic breast density, a strong risk factor for breast cancer (P=0.001). rs140068132 is located within several transcription factor-binding sites and electrophoretic mobility shift assays with MCF-7 nuclear protein demonstrate differential binding of the G/A alleles at this locus. These results highlight the importance of conducting research in diverse populations.

PMID:
25327703
PMCID:
PMC4204111
DOI:
10.1038/ncomms6260
[Indexed for MEDLINE]
Free PMC Article

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