A RARE CYP19 (AROMATASE) VARIANT MAY INCREASE THE RISK OF BREAST-CANCER

The aromatase P450 (coded by the CYP19 gene) is responsible for the ra te limiting step in the metabolism of C19 steroids to estrogens and is expressed in most breast carcinomas. A polymorphic tetranucleotide re peat (TTTA)(n) in intron 5, about 80 nucleotides downstream of exon 4 has previously been described. The allele frequencies of the polymorph ic repeat were studied in series of 182 sporadic and 185 familial brea st cancer patients as well as in 252 healthy control individuals. Five different alleles containing 7, 8, 9, 11 and 12-TTTA-repeats were det ected. A relatively rare allele (Al) containing the longest repeat (TT TA)(12) was found significantly more frequently in breast cancer patie nts than in control individuals. This indicates that individuals carry ing the Al allele of CYP19 may have an increased risk of developing br east cancer, OR 2.42 (95% confidence interval [CI] 1.03-5.80). The hig her frequency was observed in both sporadic and familial patients, alt hough when each of the groups was compared to the control group only a borderline significance was seen. A higher frequency of Al allele car riers was also found in the group of patients with positive estrogen r eceptor and progesterone receptor positive tumors. These data suggest that the CYP19 gene may be involved as a low penetrance gene in breast cancer susceptibility. (C) 1998 Chapman & Hall Ltd.