1. Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25.
- Author
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Fejerman L, Ahmadiyeh N, Hu D, Huntsman S, Beckman KB, Caswell JL, Tsung K, John EM, Torres-Mejia G, Carvajal-Carmona L, Echeverry MM, Tuazon AM, Ramirez C, Gignoux CR, Eng C, Gonzalez-Burchard E, Henderson B, Le Marchand L, Kooperberg C, Hou L, Agalliu I, Kraft P, Lindström S, Perez-Stable EJ, Haiman CA, and Ziv E
- Subjects
- Adolescent, Adult, Aged, Alleles, Biomarkers, Tumor metabolism, Breast Neoplasms metabolism, Case-Control Studies, Cell Line, Tumor, Chromosome Mapping, Female, Genetic Variation, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Mammography, Mexico, Middle Aged, Neoplasm Invasiveness, Odds Ratio, Polymorphism, Single Nucleotide, Prospective Studies, Receptors, Estrogen metabolism, Risk Factors, Young Adult, Breast Neoplasms ethnology, Breast Neoplasms genetics, Gene Expression Regulation, Neoplastic
- 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.
- Published
- 2014
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