Genome-wide Association Study of Breast Cancer in Latinas Identifies Novel Protective Variants on 6q25

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / ethnology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Case-Control Studies
  • Cell Line, Tumor
  • Chromosome Mapping
  • Female
  • Gene Expression Regulation, Neoplastic*
  • 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

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen

Grant support