Aromatase encoding by the CYP19 gene catalyzes the conversion of androgens to estrogens. In order to determine if polymorphisms of the CYP19 gene are associated with breast cancer risk, we analyzed the frequency of tetranucleotide (TTTA) tandem repeats and a 3-bp insertion (I)/deletion (D) polymorphism in intron 4 of the CYP19 gene in genomic DNA from 70 Korean breast cancer patients and 102 age-matched, healthy women. The 3-bp deletion allele was found more frequently in the breast cancer group than in the control group (p=0.001). Logistic regression analysis of the CYP 19 insertion/deletion (I/D) genotype showed a strong association between ID polymorphisms and breast cancer. The frequency of DD and ID alleles was significantly increased in the breast cancer group (DD genotype p=0.004, OR=12.81; and ID genotype p=0.005, OR=2.62). However, there were no differences in the genotype distributions of the (TTTA)n polymorphism of CYP19 between breast cancer patients and healthy controls. A positive association was noted between TTTA polymorphisms with 10 or more repeats and ER-negative tumors, as well as between lower repeat polymorphisms and ER-positive tumors (p=0.019). With respect to TTTA polymorphisms, we confirmed that the expression of aromatase in ER-positive MCF7 cells with 7-3 and 11 allele heterozygosity was significantly higher than in ER-negative MDA-MB231 cells with 11 allele homozygosity. These results suggest that 3-bp I/D polymorphisms of the CYP19 gene may be associated with breast cancer and that the (TTTA)n repeat genotype would be useful in selecting candidates for tamoxifen therapy, as well as predicting breast cancer risk in Korean women.

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