Association of single-nucleotide polymorphism (SNP) in the 5-alpha-reductase gene (SRD5A2) with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer (TC) survivors.

Abstract

4564 Background: The metabolic syndrome is more prevalent in chemotherapy (CT)-treated TC survivors in comparison with controls. Polymorphisms in the androgen receptor (AR) gene and in SRD5A2 are involved in altered androgen sensitivity, which in turn could result in the metabolic syndrome. We investigated whether a SNP in SRD5A2 and number of CAG repeats in the AR gene were associated with metabolic and cardiovascular status in TC survivors. Methods: TC survivors treated with cisplatin CT were cross-sectionally evaluated for development of cardiovascular risk factors (173 TC survivors; median age 37 yrs [range 19-59], median follow-up of 5 yrs [range 3-20]). Prevalence of metabolic syndrome (criteria AHA/NHBLI), hormonal status and vascular status (intima media thickness of the carotid artery [IMT]) were examined. SNP rs523349 (V89L) in SRD5A2 and CAG repeat numbers in the AR gene were tested against cardiovascular profile. Results: Number of CAG repeats in the AR gene was not associated with any of cardiovascular parameters. Metabolic syndrome was more prevalent in patients heterozygote or homozygote variant for rs523349 in SRD5A2compared to wild types (table). Mean IMT and urinary albumin excretion were higher in the group heterozygote or homozygote variant for rs523349. Conclusions: Metabolic syndrome in TC survivors develops more frequently in patients with a SNP (rs523349) in the gene encoding 5-alpha-reductase. These survivors have more signs of vascular damage. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and subsequent vascular changes in TC survivors and is a target for intervention. Mean (sd)/Median (range)/N (%) SRD5A2 gene Wild-type (VV) (n=91) Variant (VL/LL) (n=82) P* SNP rs523349 (V89L) Age yrs 37 (19-59) 37 (23-56) 0.39 Follow-up yrs 4.9 (3-20) 5.5 (3-20) 0.23 Metabolic syndrome 17 (19%) 27 (33%) 0.032 Body mass index kg/m2 25.3 (3.6) 25.5 (4.3) 0.71 IMT mean mm 0.57 (0.12) 0.62 (0.12) 0.026 Creatinine clearance mL/min 122 (30.8) 124 (35.5) 0.66 Albumin excretion mg/24h 3.1 (0.1-615) 5.6 (0.1-158) 0.017 * Chi2-test, t-test or MW-test used when appropriate.