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.
Highlights
The genetic contributions to breast cancer development among Latinas are not well understood
We found that the minor allele is more protective against ER-negative disease and that it is associated with decreased mammographic density
The rs140068132/rs147157845 single-nucleotide polymorphisms (SNPs) are relatively common in Latin American populations, ranging between 5 and 15% depending on the proportion of Indigenous American ancestry of the region but are rare (o2%) or absent in other groups
Summary
The genetic contributions to breast cancer development among Latinas are not well understood. Among Latina women, those with a high proportion of Indigenous American ancestry are at a lower risk of developing breast cancer[2,3]. This association could result from the correlation between genetic ancestry and environmental risk factors[4], as well as genetics[5]. We report the discovery of a genome-wide significant breast cancer-protective variant of Indigenous American origin (rs140068132), located 50 of the Estrogen Receptor 1 gene (ESR1; 6q25 region)
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