A rare CYP19 (aromatase) variant may increase the risk of breast cancer.

The aromatase P450 (coded by the CYP19 gene) is responsible for the rate limiting step in the metabolism of C19 steroids to estrogens and is expressed in most breast carcinomas. A polymorphic tetranucleotide repeat (TTTA)n in intron 5, about 80 nucleotides downstream of exon 4 has previously been described. The allele frequencies of the polymorphic repeat were studied in series of 182 sporadic and 185 familial breast cancer patients as well as in 252 healthy control individuals. Five different alleles containing 7, 8, 9, 11 and 12-TTTA-repeats were detected. A relatively rare allele (A1) containing the longest repeat (TTTA)12 was found significantly more frequently in breast cancer patients than in control individuals. This indicates that individuals carrying the A1 allele of CYP19 may have an increased risk of developing breast cancer, OR 2.42 (95% confidence interval [CI] 1.03-5.80). The higher frequency was observed in both sporadic and familial patients, although when each of the groups was compared to the control group only a borderline significance was seen. A higher frequency of A1 allele carriers was also found in the group of patients with positive estrogen receptor and progesterone receptor positive tumors. These data suggest that the CYP19 gene may be involved as a low penetrance gene in breast cancer susceptibility.