TA repeat polymorphism of the 5 alpha-reductase gene and breast cancer

There is increasing evidence that androgens play a significant role in the development and progression of breast cancer. 5 alpha-Reductase (SRD5A2) is an enzyme that is expressed in androgen-dependent tissues, and it catalyze s the reduction of testosterone to its more bioactive form, dihydrotestoste rone, which then transactivates a number of genes. One of these genes encod es for prostate-specific antigen (PSA), a favorable prognostic factor in br east cancer. The 3' untranslated region of the SRD5A2 gene contains either no TA repeats [(TA)(0)] or 9 [(TA)(9)] or 18 [(TA)(18),] repeats. Variation s in the length of these dinucleotide repeats have been reported to influen ce the enzymatic activity of SRD5A2. In this study, we determined the TA genotypes in DNA from 141 well-characte rized breast tumors and in DNA from whole blood of 70 women without cancer. The presence of TA genotypes was then associated with tumor cytosolic PSA concentrations and with clinicopathological variables, including disease-fr ee survival and overall survival, Three genotypes, (TA)(0) homozygote, (TA) (0)/(TA)(9) heterozygote, and (TA)(9) homozygote, were identified. No (TA)( 18) alleles were detected in any of the two patient groups. A statistically significant association between high PSA concentrations and (TA)(0)/(TA)(9 ) or (TA)(9) genotypes was observed (P = 0.004). (TA)(0)/(TA)(9) or (TA)(9) genotypes were found less frequently in patients at stage III or IV diseas e. TA genotypes were not associated with other clinicopathological variable s by contingency table analysis. Patients with (TA)(0)/(TA)(9) or (TA)(9) r epeats, when compared to those with genotypes homozygous for the (TA)(0) al lele, showed a significant reduction in the risk for relapse (P = 0.043). L ong-term studies are needed to investigate the relevance of this polymorphi sm to breast cancer susceptibility.