[Case-control study of the genes of receptors of the androgens of vitamin-D and of 5-alphareductase in a population...

The proliferation of prostate cells appears to be influenced by two steroidal hormones: testosterone and vitamin D, whose action appears to mediated by their respective receptors. The genes coding for these two receptors and the gene coding for 5-alpha-reductase (enzyme involved in testosterone metabolism) have been identified as candidate genes for prostate cancer predisposition. Previous epidemiological and genetic susceptibility studies have reported controversial results concerning the role of these genes on prostate cancer incidence in various populations. The objective of this study was to determine the possible association in this population between polymorphisms of these genes, and the clinical and pathological stage and grade of prostate cancer.

This case-control epidemiogenetic study was based on 253 subjects living in Martinique. Prostate cancer is the most frequent cancer in men and the leading cause of cancer death in Martinique. Its incidence is 80 per 100,000 inhabitants (world population standardized rates), which makes Martinique one of the most severely affected regions in the world with an incidence close to that of Afro-Americans. Cases and controls were recruitedfrom the hospital and general populations. The following gene polymorphisms were evaluated: the androgen receptor (AR) was studied by microsatellites of the CAG codon repeat domain; the vitamin D receptor (VDR) gene was studied on poly(A) sequences of the 3'-UTR region; 5a-reductase II (SRD5A2) was studied by poly(TA) microsatellites. The odds-ratio (OR) was estimated by logistic regression with integration of clinical and biological parameters.

Our results for the androgen receptor showed an association between the presence of more than 20 CAG repeats and localized or low-grade forms. A risk related to the heavy allele of VDR was observed in advanced and low-grade forms (PSA-T > 20 ng/ml). Lastly, no 5a-reductase polymorphism distinguishing cases from controls was observed.

This study demonstrated results that differ from those observed for other populations with a similar ethnic origin. For AR and VDR genes, the presence of a heavy allele is associated with an increased risk of developing prostate cancer with a poor prognosis. No high-risk group was identified according to 5a-reductase gene polymorphism.