Genetic polymorphism of estrogen metabolizing enzymes in Siberian women with breast cancer.

Allelic variants of cytochrome P450: CYP1A1, CYP1A2, CYP19 (aromatase), and the II-phase enzyme sulfotransferase 1A1 (SULT1A1) genes are associated with a high risk of hormone-dependent cancers. We estimated the frequency of these allelic variants in the female population of the Novosibirsk district and their association with the elevated risk of breast cancer. A DNA bank of patients with gynecologic oncology, patients with breast cancer (n = 335), and healthy women (n = 530) was created, and the following single-nucleotide polymorphisms were examined: CYP1A1 M1 polymorphism, that is, T264-C transition in the 30-noncoding region; CYP1A2*1F polymorphism, that is, C734-A transversion in the CYP1A2 gene; C-T transition (Arg264Cys) in exon 7 of CYP19; and SULT1A1*2 polymorphism, that is, G638-A transition (Arg213His) in the SULT1A1 gene. The results of our study indicate that women with mutant allele C and genotypes C/T, C/C of the CYP1A1 gene, wild-allele C, and genotype C/C of the CYP1A2 gene, mutant allele A and genotypes A/G, A/A of the SULT1A1 gene have an increased risk of development of breast cancer. Women with body mass index ≥ 30 and the heterozygous genotype C/T of the CYP19 gene have an increased risk of breast cancer. The CYP1A2 heterozygous variant genotype C/A is associated with an increased risk of an estrogen receptor (ER(+)) tumor.