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Shatalova EG , Loginov VI , Bragar EA , Kazubskaja TP , Sudomoina MA , Blanchard RL , Favorova OO
Association of polymorphisms in SULTIAI and UGTIAI genes with breast cancer risk and phenotypes in Russian women
MOLECULAR BIOLOGY. 2006 Mar-Apr;40(2) :263-270
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AbstractEstrogens are critical for breast cancer initiation and development. Sulfotransferase 1A1 (SULT1A1) and UDP-glucuronosyltransferase 1A1 (UGT1A1) conjugate and inactivate both estrogens and their metabolites, thus preventing estrogen-mediated mitosis and mutagenesis. SULT1A1 and UGT1A1 genes are both polymorphic,and different alleles encode functionally different allozymes. We hypothesize that low activity alleles SULT1A1*2 and UGT1A1*28 are associated with the higher risk for breast cancer and more severe breast tumor phenotypes. We performed a case-control study, which included 119 women of Russian ancestry with breast cancer and 121 age-matched Russian female controls. We used PCR, followed by pyrosequencing to determine SULT1A1 and UGT1A1 genotypes. Our data showed that UGT1A1*28 allele was presented at a higher frequency than the wild type UGT1A1*1 allele in breast cancer patients as compared to controls (p = 0.002, OR = 1.79, CI 1.23-2.63). Consistently, the frequency o! f genotypes that contain the UGT1A1*28 allele in the homozygous or heterozygous state was greater than the frequency of the wild type UGT1A1*1/*1 genotype in breast cancer patients as compared to controls (p = 0.003, OR = 4.00, CI 1.49-11.11 and p = 0.014, OR = 2.04, CI 1.14-3.57, respectively). The group of individuals, carrying the UGT1A1*28 allele in the homo- or heterozygous state also presented larger breast tumors (>2 cm) as compared to the group with high enzymatic activity genotypes p = 0.011, OR = 3.44, CI 1.42-8.36). No association was observed between any of the SULT1A1 genotypes and breast cancer risk or phenotypes. Our data suggest that UGT1A1 but not SULT1A1 genotype might be important for breast cancer risk and phenotype in Russian women.