Exposure to
sex hormones is a major risk factor for
breast cancer and current treatments include
hormone modifying drugs, among them
aromatase inhibitors. We studied the association of
CYP19 (Val(80) and [TTTA](n)) polymorphisms, the gene translated to
aromatase, and the risk of
breast cancer in BRCA carriers and noncarriers. The study consisted of 958
cancer cases and 931 healthy controls, including 474 carriers and 1,415 noncarriers. Cases and controls came from a population-based study of
breast cancer in Israel, enriched with BRCA carriers from a clinical familial
cancer service. Val(80) G/G genotype was associated with significantly increased risk of
breast cancer compared with the Val(80) A/A genotype in BRCA1 carriers ages <50 years (odds ratio, 2.81; 95% confidence interval, 1.09-7.22; P = 0.032) but not in BRCA2 carriers or noncarriers of any age. A similar magnitude suggestive association, although nonstatistically significant, was found between Val(80) polymorphism and
estrogen receptor-negative status of the
breast tumors. A common haplotype composed of the Val(80) G allele and three haplotype-tagging single nucleotide polymorphisms (rs727479, rs10046, and rs4646) in the
CYP19 coding region showed a trend to association with
breast cancer risk in BRCA1 carriers ages <50 years. Published expression data show higher
estrogen levels with higher repeats in [TTTA](n) found in linkage disequilibrium with Val(80). The present study suggests that the
CYP19 Val(80) polymorphism and a haplotype that includes this polymorphism are associated with increased
breast cancer risk in young women with BRCA1 mutations.