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+ACA BRCA1 promoter polymorphism confers increased risk of breast cancer among African‐American women
Author(s) -
White Kristen K.,
Basta Patricia V.,
Booker Jessica K.,
Millikan Robert C.,
Coleman William B.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.898.25
Subject(s) - breast cancer , odds ratio , genotype , genotyping , medicine , allele , oncology , cancer , genetics , biology , gene
We previously identified an ACA insertion polymorphism (+ACA) in the BRCA1 promoter that creates a consensus binding site (AACAACAC) for the FAC1 transcriptional repressor (located 600 bp upstream of the exon 1a transcriptional start site). Expression of FAC1 in individuals that carry the +ACA polymorphism may result in loss of BRCA1 expression, contributing to breast cancer susceptibility. Genotyping of 589 women from the Carolina Breast Cancer Study (308 cases, 281 controls) yielded higher +ACA allele frequencies among African‐American (AA) cases (27%) compared to AA controls (17%, P = 0.0005), but there was no significant difference among Caucasian (CC) cases and controls (34% versus 37%, P = 0.50). Genotype distributions among AA and CC cases and controls showed no significant departures from Hardy Weinberg equilibrium. Age‐adjusted odds ratios (ORs) for breast cancer among AA women were 4.6 (95% CI 1.3–17.0) for +ACA/+ACA and 1.6 (95% CI 1.0–2.7) for wt/+ACA compared to wt/wt homozygotes. Among CC women, the relevant ORs were 0.7 (95% CI 0.3–1.5) for +ACA/+ACA and 1.1 (95% CI 0.7–1.8) for wt/+ACA. These results suggest a statistically significant association between the +ACA BRCA1 promoter polymorphism and breast cancer susceptibility among AA women. Support: NIH CA78343, CA58223, CA16086; Komen Foundation BCTR0100575, Friends For an Earlier Breast Cancer Test.