Genetic variants on chromosome 5p12 are associated with risk of breast cancer in African American women: the Black Women’s Health Study |
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Authors: | Edward A Ruiz-Narvaez Lynn Rosenberg Charles N Rotimi L Adrienne Cupples Deborah A Boggs Adebowale Adeyemo Yvette C Cozier Lucile L Adams-Campbell and Julie R Palmer |
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Affiliation: | (1) Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA 02215, USA;(2) Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA;(3) Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA;(4) Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA;(5) Georgetown University Medical Center, Washington, DC, USA; |
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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. |
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