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Genetic variants on chromosome 5p12 are associated with risk of breast cancer in African American women: the Black Women's Health Study

Author:
  • Kerryn W. Reding
  • Jonine L. Bernstein
  • Bryan M. Langholz
  • Leslie Bernstein
  • Robert W. Haile
  • Colin B. Begg
  • Charles F. Lynch
  • Patrick Concannon
  • Åke Borg
  • Sharon N. Teraoka
  • Therese Törngren
  • Anh Diep
  • Shanyan Xue
  • Lisbeth Bertelsen
  • Xiaolin Liang
  • Anne S. Reiner
  • Marinela Capanu
  • Kathleen E. Malone
Publishing year: 2010
Language: English
Pages: 491-498
Publication/Series: Breast Cancer Research and Treatment
Volume: 123
Issue: 2
Document type: Journal article
Publisher: Springer

Abstract english

Two single nucleotide polymorphisms (SNPs), rs4415084, and rs10941679 on chromosome 5p12 were associated with risk of breast cancer in a recent genome-wide association study (GWAS) of women of European ancestry. Both SNPs are located in a large high-LD region and the causal variant(s) are still unknown. We conducted a nested case-control study in a cohort of African American women to replicate and narrow the region carrying the causal variant(s). We evaluated 14 tagging SNPs in a 98 kb LD block surrounding the index SNPs in 886 breast cancer cases and 1,089 controls from the Black Women's Health Study. We used the Cochran-Armitage trend test to assess association with breast cancer risk. Odds ratios were derived from logistic regression analyses adjusted for potential confounders including percent European admixture. We confirmed the reported association of rs4415084 SNP with overall risk of breast cancer (P = 0.06), and, as in the original study, observed a stronger association with estrogen receptor positive tumors (P = 0.03). We identified four other SNPs (rs6451770, rs12515012, rs13156930, and rs16901937) associated with risk of breast cancer at the nominal alpha value of 0.05; all of them were located in a 59 kb HapMap YRI LD block. After correction for multiple testing, the association with SNP rs16901937 remained significant (P permutated = 0.038). The G allele was associated with a 21% increased risk of breast cancer overall and with a 32% increase in tumors positive for both estrogen and progesterone receptors. The present results from an African ancestry (AA) population confirm the presence of breast cancer susceptibility genetic variants in the chromosome 5p12 region. We successfully used the shorter range of LD in our AA sample to refine the localization of the putative causal variant.

Keywords

  • Cancer and Oncology
  • Contralateral
  • Chemotherapy
  • Breast cancer
  • BRCA2
  • Adjuvant therapy
  • BRCA1
  • Counter-matching
  • Tamoxifen

Other

Published
  • ISSN: 1573-7217
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90