Shatalova E G, Loginov V I, Braga E A, Kazubskaia T P, Sudomoina M A, Blanchard R L, Favorova O O
Mol Biol (Mosk). 2006 Mar-Apr;40(2):263-70.
Estrogens 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 SULT1A12 and UGT1A128 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 UGT1A128 allele was presented at a higher frequency than the wild type UGT1A11 allele in breast cancer patients as compared to controls (p = 0.002, OR = 1.79, CI 1.23-2.63). Consistently, the frequency of genotypes that contain the UGT1A128 allele in the homozygous or heterozygous state was greater than the frequency of the wild type UGT1A11/1 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 UGT1A128 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.
雌激素对乳腺癌的起始和发展至关重要。磺基转移酶1A1（SULT1A1）和尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT1A1）可结合雌激素及其代谢产物并使其失活，从而防止雌激素介导的有丝分裂和诱变。SULT1A1和UGT1A1基因均具有多态性，不同的等位基因编码功能不同的同工酶。我们推测，低活性等位基因SULT1A12和UGT1A128与乳腺癌风险较高及更严重的乳腺肿瘤表型相关。我们进行了一项病例对照研究，纳入了119名俄罗斯裔乳腺癌女性和121名年龄匹配的俄罗斯女性对照。我们采用聚合酶链反应（PCR），随后进行焦磷酸测序来确定SULT1A1和UGT1A1基因型。我们的数据显示，与对照组相比，乳腺癌患者中UGT1A128等位基因的出现频率高于野生型UGT1A11等位基因（p = 0.002，比值比[OR] = 1.79，置信区间[CI] 1.23 - 2.63）。同样，与对照组相比，乳腺癌患者中纯合或杂合状态下含有UGT1A128等位基因的基因型频率高于野生型UGT1A11/1基因型频率（分别为p = 0.003，OR = 4.00，CI 1.49 - 11.11和p = 0.014，OR = 2.04，CI 1.14 - 3.57）。与具有高酶活性基因型的组相比，纯合或杂合状态下携带UGT1A128等位基因的个体组也表现出更大的乳腺肿瘤（>2 cm）（p = 0.011，OR = 3.44，CI 1.42 - 8.36）。未观察到任何SULT1A1基因型与乳腺癌风险或表型之间存在关联。我们的数据表明，对于俄罗斯女性的乳腺癌风险和表型而言，UGT1A1基因型而非SULT1A1基因型可能很重要。
