Polymorphisms in the human aromatase cytochrome P450 gene (CYP19) and breast cancer risk

The aromatase enzyme catalyses the conversion of androgens to oestrogens in the oestrogen biosynthesis pathway. Because increased exposure to oestroge ns is considered to be a risk factor for breast cancer, the human aromatase gene (CYP19) is a plausible candidate for Pow penetrance breast cancer sus ceptibility, Preliminary reports have suggested that specific alleles of a TTTA repeat may be associated with differences in breast cancer risk. We ha ve identified two new polymorphisms in the CYP19 gene: a TCT insertion/dele tion in intron 4 and a G-->T substitution in intron 6, which have rare alle le frequencies of 0.35 and 0.45, respectively, in the British population, C omparison was made between the frequencies of these alleles and those of th e TTTA repeat in up to 599 breast cancer cases and 433 normal controls from the East Anglian, British population. We found strong linkage disequilibri um between the alleles of these three loci, but no significant association of any alleles with breast cancer risk. The maximum odds ratios observed we re: 1.03 (95% CI 0.68-1.55) for the intron 4 TCT insertion/deletion polymor phism [del/del versus ins/ins]; 1.56 (95% CI 0.63-3.83) for the intron 4 [T TTA]lo allele; 1.29 (95% CI 0.75-2.21) for the intron 6 G-->T polymorphism [TT versus GG], We conclude that the CYP19 gene has no major role in common breast cancer incidence in the British population.