Basic scienceV89L polymorphism of type-2, 5-alpha reductase enzyme gene predicts prostate cancer presence and progression☆
Section snippets
Study subjects
To examine the effects of the SRD5A2 polymorphism on prostate cancer risk and progression, we used two independent study samples because of the different requirements for the control population. The first study determined the probability of the presence of prostate cancer by the SRD5A2 polymorphism by comparing patients with and without prostate cancer. The second study determined the probability of prostate cancer progression by the SRD5A2 polymorphism by comparing patients with established
Prostate cancer risk
Of the 320 men, 158 patients (49.4%) were found at biopsy to have prostate cancer (patients). Of the 162 men with no evidence of cancer (controls), 81 (50%) had normal prostatic tissue, 35 (22%) had evidence of inflammation, benign prostatic hyperplasia, or cellular atypia, and 46 (28%) had prostatic intraepithelial neoplasia. The mean age of the patients and controls was 66.6 and 65.5 years, respectively (P = 0.22). The mean PSA level of the patients and controls was 14.6 and 10.7 ng/mL,
Comment
This study is the first that relates a host susceptibility factor to both prostate cancer risk and progression on the basis of biologic observations relating 5-alpha reductase-2 activity to this polymorphism. Febbo et al.22 did not find a positive association between prostate cancer risk and the SRD5A2 V89L polymorphism. However, all patients with prostate cancer were selected, including patients who presented with metastases and those who did not undergo PSA screening, in sharp contrast to our
Conclusions
The results of these two studies demonstrate that, after controlling for established factors for prostate cancer risk and progression, patients who have the V allele of the SRD5A2 gene have a twofold increase in the risk of prostate cancer development and an additional twofold increase in the risk of progression compared with patients with the L/L genotype.
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Cited by (88)
Genetic variation: Effect on prostate cancer
2014, Biochimica et Biophysica Acta - Reviews on CancerPolymorphisms in androgen signaling pathway predisposing to prostate cancer
2012, Molecular and Cellular EndocrinologyCitation Excerpt :Based on performed meta-analyses there is reason to believe that V89L it is not associated with overall PCa risk. A few studies have shown evidence that A49T and V89L may have an affect on the clinical behavior or outcome (Jaffe et al., 2000; Nam et al., 2001; Soderstrom et al., 2002; Cussenot et al., 2007) but these observations are again contradictory (Latil et al., 2001; Cicek et al., 2004; Mononen et al., 2006). The (TA)n dinucleotide repeat (rs10529926) on the 3′UTR region in the SRD5A2 gene was first described by Davis and Russell (1993).
Prognostic significance of genetic polymorphisms on prostate-specific antigen recurrence after a radical prostatectomy
2012, Urological ScienceCitation Excerpt :In addition, the A49T variant was overrepresented in two poor prognostic groups, which were correlated with reduced rates of biochemical disease-free survival.41 Nam and colleagues42 studied SRD5A2 V89L polymorphisms in 318 Canadian men who had undergone a radical prostatectomy. They found that the OR for progression in patients with at least one V allele (V/L or V/V) was 3.32 (95% CI = 1.67∼6.62, p = 0.0006) compared with patients with the L/L genotype.42
Association among polymorphisms in the steroid 5α-reductase type II (SRD5A2) gene, prostate cancer risk, and pathologic characteristics of prostate tumors in an Ecuadorian population
2009, Cancer Genetics and CytogeneticsCitation Excerpt :Two previous studies [12,16] that found the V allele to be associated with an increased risk of prostate cancer failed to show an association between the V89L polymorphism and the pathologic characteristics of tumors. Nam et al. [11] found the V allele associated with an increased risk of progression, but not with a specific pathological trait. In opposition, other studies found the L allele to be associated with more aggressive tumors and with a higher progression of the disease [15,22,23].
Shorter CAG repeats in androgen receptor and non-GG genotypes in prostate-specific antigen loci are associated with decreased risk of benign prostatic hyperplasia and prostate cancer
2008, Cancer LettersCitation Excerpt :This enzyme helps to irreversibly convert testosterone to the more potent and active dihydrotestosterone (DHT) as it enters the prostate cell. The gene SRD5A2 has two SNPs which have been studied in relation to PC, the valine to leucine substitution at codon 89 (V89L) [22–24] and A49T [25,26] which are suggested to alter DHT levels and consequently increase susceptibility to PC. The V89L polymorphism was also associated with BPH risk.
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This study was supported by grant 009112 from the National Cancer Institute of Canada. Dr. Nam was supported by a research fellowship from the Surgical Scientist Program, Department of Surgery, University of Toronto, Toronto, Canada.