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Published on: November 2, 2013
Polymorphic markers in the SRD5A2 gene and prostate cancer risk: a population-based case-control study
A W Hsing1, C Chen, A P Chokkalingam
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20852-7234, USA. hsinga@exchange.nih.gov
This study investigated the steroid 5alpha-reductase type II gene (SRD5A2) and prostate cancer risk in China. While no significant associations were found, certain genotypes correlated with androgen levels, suggesting a potential role in population risk differences.
Area of Science:
- Genetics
- Oncology
- Endocrinology
Background:
- Steroid 5alpha-reductase type II enzyme activity, encoded by SRD5A2, is hypothesized to influence prostate cancer risk.
- Population variations in this enzyme's activity may explain racial/ethnic disparities in prostate cancer incidence.
Purpose of the Study:
- To investigate the association between SRD5A2 gene polymorphisms and prostate cancer risk in a Chinese population.
- To explore relationships between SRD5A2 genotypes and serum androgen levels.
Main Methods:
- A case-control study in China involving 191 prostate cancer cases and 304 controls.
- Genotyping of four SRD5A2 polymorphic markers: A49T, V89L, R227Q, and a (TA)n dinucleotide repeat.
- Measurement of serum androgen levels in relation to genotypes.
Main Results:
- All subjects had wild-type A49T and nearly all had wild-type R227Q genotypes.
- V89L genotypes showed varied prevalence; LL genotype was associated with a nonsignificant 12% reduced risk and altered testosterone and 5alpha-diol glucuronide levels.
- Heterozygosity for the (TA)0 allele of the (TA)n marker showed a nonsignificant risk reduction and higher dihydrotestosterone levels.
Conclusions:
- Observed V89L genotype frequencies and associations with androgen levels support the hypothesis that lower 5alpha-reductase activity genotypes are more common in low-risk populations.
- No statistically significant associations between SRD5A2 polymorphisms and prostate cancer risk were found, but a small effect cannot be excluded.
- Larger studies are needed to clarify the role of SRD5A2 gene diversity in explaining prostate cancer risk disparities.
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