Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer

Dezheng Huo, Ye Feng, Stephen Haddad, Yonglan Zheng, Song Yao, Yoo Jeong Han, Temidayo O. Ogundiran, Clement Adebamowo, Oladosu Ojengbede, Adeyinka G. Falusi, Wei Zheng, William Blot, Qiuyin Cai, Lisa Signorello, Esther M. John, Leslie Bernstein, Jennifer J. Hu, Regina G. Ziegler, Sarah Nyante, Elisa V. BanderaSue A. Ingles, Michael F. Press, Sandra L. Deming, Jorge L. Rodriguez-Gil, Katherine L. Nathanson, Susan M. Domchek, Timothy R. Rebbeck, Edward A. Ruiz-Narváez, Lara E. Sucheston-Campbell, Jeannette T. Bensen, Michael S. Simon, Anselm Hennis, Barbara Nemesure, M. Cristina Leske, Stefan Ambs, Lin S. Chen, Frank Qian, Eric R. Gamazon, Kathryn L. Lunetta, Nancy J. Cox, Stephen J. Chanock, Laurence N. Kolonel, Andrew F. Olshan, Christine B. Ambrosone, Olufunmilayo I. Olopade, Julie R. Palmer, Christopher A. Haiman

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina's HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P=1.8×10 -8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR=1.30; P=2.4×10 -10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR=1.34; P=2.2×10 -8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.

Original languageEnglish (US)
Pages (from-to)4835-4846
Number of pages12
JournalHuman molecular genetics
Volume25
Issue number21
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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