Journal Article

Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry

Dezheng Huo, Yonglan Zheng, Temidayo O. Ogundiran, Clement Adebamowo, Katherine L. Nathanson, Susan M. Domchek, Timothy R. Rebbeck, Michael S. Simon, Esther M. John, Anselm Hennis, Barbara Nemesure, Suh-Yuh Wu, M.Cristina Leske, Stefan Ambs, Qun Niu, Jing Zhang, Nancy J. Cox and Olufunmilayo I. Olopade

in Carcinogenesis

Volume 33, issue 4, pages 835-840
Published in print April 2012 | ISSN: 0143-3334
Published online February 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs093
Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry

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Multiple breast cancer susceptibility loci have been identified in genome-wide association studies (GWAS) in populations of European and Asian ancestry using array chips optimized for populations of European ancestry. It is important to examine whether these loci are associated with breast cancer risk in women of African ancestry. We evaluated 25 single nucleotide polymorphisms (SNPs) at 19 loci in a pooled case–control study of breast cancer, which included 1509 cases and 1383 controls. Cases and controls were enrolled in Nigeria, Barbados and the USA; all women were of African ancestry. We found significant associations for three SNPs, which were in the same direction and of similar magnitude as those reported in previous fine-mapping studies in women of African ancestry. The allelic odds ratios were 1.24 [95% confidence interval (CI): 1.04–1.47; P = 0.018] for the rs2981578-G allele (10q26/FGFR2), 1.34 (95% CI: 1.10–1.63; P = 0.0035) for the rs9397435-G allele (6q25) and 1.12 (95% CI: 1.00–1.25; P = 0.04) for the rs3104793-C allele (16q12). Although a significant association was observed for an additional index SNP (rs3817198), it was in the opposite direction to prior GWAS studies. In conclusion, this study highlights the complexity of applying current GWAS findings across racial/ethnic groups, as none of GWAS-identified index SNPs could be replicated in women of African ancestry. Further fine-mapping studies in women of African ancestry will be needed to reveal additional and causal variants for breast cancer.

Journal Article.  5063 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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