Data from Polymorphisms in the <i>TOX3/LOC643714</i> Locus and Risk of Breast Cancer in African-American Women

Abstract

<div>Abstract<p><b>Background:</b> The rs3803662 single nucleotide polymorphism (SNP) in the <i>TOX3/LOC643714</i> region was identified as a breast cancer susceptibility genetic variant in recent genome-wide association studies of women of European ancestry and has been replicated in other populations of European ancestry. The position of the causal variant tagged by the rs3803662 marker is still unknown. In fact, because the rs3803662 polymorphism is located between the <i>TOX3</i> and the <i>LOC643714</i> loci, it is unclear which gene is the one causally related to the risk of breast cancer. Because linkage disequilibrium blocks are smaller in populations of African ancestry, fine-mapping in African ancestry samples might be an effective approach to narrowing the position of the causal variant(s) in the <i>TOX3/LOC643714</i> locus.</p><p><b>Methods:</b> We evaluated a total of 60 tagging SNPs throughout the <i>TOX3/LOC643714</i> region in a nested case-control study of breast cancer within the Black Women's Health Study, which included 906 cases and 1,111 controls.</p><p><b>Results:</b> No significant association was found for the rs3803662 SNP. However, four other SNPs (rs3104746, rs3112562, rs3104793, and rs8046994), all of them located in the <i>LOC643714</i> gene, were associated with risk of breast cancer. The strongest association was observed for rs3104746: each copy of the A-rs3104746 allele was associated with a 23% higher risk of breast cancer (odds ratios, 1.23; 95% confidence intervals, 1.05-1.44; <i>P</i> = 0.009).</p><p><b>Conclusions:</b> Our results confirm the association observed in genome-wide association studies of European ancestry populations.</p><p><b>Impact:</b> The results narrow the locus to a smaller linkage disequilibrium block in the <i>LOC643714</i> gene. Cancer Epidemiol Biomarkers Prev; 19(5); 1320–7. ©2010 AACR.</p></div>