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Shatalova Ekaterina G , Walther Susan E , Favorova Olga O , Rebbeck Timothy R , Blanchard Rebecca L
Genetic polymorphisms in human SULT1A1 and UGT1A1 genes associate with breast tumor characteristics: A case-series study
Breast Cancer Research. 2005 ;7(6) :R909-R921
PMID: AN 2005:1215056
AbstractIntroduction Estrogens are important in breast cancer development. SULT1A1 and UGT1A1 catalyze estrogen metab. and are polymorphic. The SULT1A1*2 protein exhibits low activity, and a TA repeat within the UGT1A1 promoter alters the level of expression of the protein. We hypothesized that the SULT1A1*2 allozyme has decreased capacity to sulfate estrogens, that the SULT1A1*2 allele conferred increased capacity of cells to proliferate in response to estrogens, and that individuals with the variant SULT1A1 and UGT1A1 genotypes exhibited different breast tumor characteristics. Methods The capacity for SULT1A1*2 to sulfate 17b-estradiol and the capacity for cells expressing SULT1A1*1 or SULT1A1*2 to proliferate in response to 17b-estradiol was evaluated. A case-series study was performed in a total of 210 women with incident breast cancer, including 177 Caucasians, 25 African-Americans and eight women of other ethnic background. The SULT1A1 and UGT1A1 genotypes were detd. and a logistic regression model was used to analyze genotype-phenotype assocns. Results We detd. that the SULT1A1*1/*1 high-activity genotype was assocd. with tumor size ?2 cm (odds ratio = 2.63, 95% confidence interval = 1.25-5.56, P = 0.02). Individuals with low-activity UGT1A1 genotypes (UGT1A1*28/*28 or UGT1A1*28/*34) were more likely to have an age at diagnosis >=60 years (odds ratio = 3.70, 95% confidence interval = 1.33-10.00, P = 0.01). Individuals with both SULT1A1 and UGT1A1 high-activity genotypes had low tumor grade (odds ratio = 2.56, 95% confidence interval = 1.04-6.25, P = 0.05). Upon stratification by estrogen receptor status, significant assocns. were obsd. predominantly in estrogen receptor-neg. tumors. Conclusion The data suggest that genetic variation in SULT1A1 and UGT1A1 may influence breast cancer characteristics and might be important for breast cancer prognosis. [on SciFinder (R)]
Notes14 Mammalian Pathological Biochemistry Department of Pharmacology,Fox Chase Cancer Center,Philadelphia,PA,USA. Journal; Online Computer File 1465-542X written in English.