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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

Reding, Kerryn W.; Bernstein, Jonine L.; Langholz, Bryan M.; Bernstein, Leslie; Haile, Robert W.; Begg, Colin B.; Lynch, Charles F.; Concannon, Patrick; Borg, Åke LU and Teraoka, Sharon N., et al. (2010) In Breast Cancer Research and Treatment 123(2). p.491-498
Abstract
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... (More)
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. (Less)
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keywords
Contralateral, Chemotherapy, Breast cancer, BRCA2, Adjuvant therapy, BRCA1, Counter-matching, Tamoxifen
in
Breast Cancer Research and Treatment
volume
123
issue
2
pages
491 - 498
publisher
Springer
external identifiers
  • wos:000280807900019
  • scopus:77956186324
ISSN
1573-7217
DOI
10.1007/s10549-010-0769-3
language
English
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yes
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a99b97e2-baa7-4c9c-99f5-41d90b03d4c0 (old id 1676909)
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2010-09-21 10:15:50
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2018-05-29 09:44:02
@article{a99b97e2-baa7-4c9c-99f5-41d90b03d4c0,
  abstract     = {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.},
  author       = {Reding, Kerryn W. and Bernstein, Jonine L. and Langholz, Bryan M. and Bernstein, Leslie and Haile, Robert W. and Begg, Colin B. and Lynch, Charles F. and Concannon, Patrick and Borg, Åke and Teraoka, Sharon N. and Törngren, Therese and Diep, Anh and Xue, Shanyan and Bertelsen, Lisbeth and Liang, Xiaolin and Reiner, Anne S. and Capanu, Marinela and Malone, Kathleen E.},
  issn         = {1573-7217},
  keyword      = {Contralateral,Chemotherapy,Breast cancer,BRCA2,Adjuvant therapy,BRCA1,Counter-matching,Tamoxifen},
  language     = {eng},
  number       = {2},
  pages        = {491--498},
  publisher    = {Springer},
  series       = {Breast Cancer Research and Treatment},
  title        = {Genetic variants on chromosome 5p12 are associated with risk of breast cancer in African American women: the Black Women's Health Study},
  url          = {http://dx.doi.org/10.1007/s10549-010-0769-3},
  volume       = {123},
  year         = {2010},
}