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  • Title: A49T, V89L and TA repeat polymorphisms of steroid 5alpha-reductase type II and breast cancer risk in Japanese women.
    Author: Yang C, Hamajima N, Iwata H, Saito T, Matsuo K, Hirose K, Inoue M, Takezaki T, Tajima K.
    Journal: Breast Cancer Res; 2002; 4(4):R8. PubMed ID: 12100746.
    Abstract:
    BACKGROUND: Breast cancer is hormone related, as are cancers of the endometrium, ovary, and prostate. Several studies have suggested that higher extracellular levels of androgens are associated with breast cancer risk, while biological evidence indicates that androgens are protective. The codon 49 alanine to threonine substitution (A49T), codon 89 valine to leucine substitution (V89L) and TA repeat polymorphisms of the steroid 5alpha-reductase type II (SRD5A2) gene are considered functional with respect to enzyme activity converting testosterone into dihydrotestosterone. To test the hypothesis that these three polymorphisms are associated with risk of breast cancer, a case-control study was conducted with patients of Aichi Cancer Center Hospital. METHODS: The cases were 237 patients histologically diagnosed with breast cancer, and the controls were 185 noncancer outpatients. DNA from peripheral blood was genotyped by PCR methods. RESULTS: The threonine allele of A49T was not found in our subjects. Compared with the V/V genotype of V89L, the L/L genotype was associated with a decreased risk (crude odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.36-1.05). This was also the case for the TA(9/9) genotype, with an OR of 0.58 (95% CI = 0.13-2.63) relative to TA(0/0). Among women with the TA(0/0) genotype, however, the OR for the L/L genotype was 0.46 (95% CI = 0.24-0.88) compared with the V/V genotype, and those with the V/V and TA(0/0) genotypes had the highest risk. The haplotype with the L and TA(9) repeat alleles was not found. CONCLUSION: This study is the first to our knowledge focusing on Japanese women, suggesting that SRD5A2 polymorphisms might have an association with breast cancer risk. Further large-sample studies will be required to confirm the association and to assess any interactions with environmental factors.
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