title: Single-nucleotide polymorphism in the 5-α-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors.
abstract: OBJECTIVE
  Chemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-α-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated whether single-nucleotide polymorphisms (SNPs) rs523349 (V89L) and rs9282858 (A49T) in SRD5A2 are associated with cardiometabolic status in testicular cancer survivors.
  
  
  METHODS
  In 173 chemotherapy-treated testicular cancer survivors, hormone levels and cardiometabolic status were evaluated cross-sectionally (median 5 years [range 3-20] after chemotherapy) and correlated with SNPs in SRD5A2.
  
  
  RESULTS
  The metabolic syndrome was more prevalent in survivors who were homozygous or heterozygous variant for SRD5A2 rs523349 compared to wild type (33% versus 19%, P = 0.032). In particular, patients with lower testosterone levels (<15 nmol/l) and a variant genotype showed a high prevalence of the metabolic syndrome (66.7%). Mean intima-media thickness of the carotid artery and urinary albumin excretion, both markers of vascular damage, were higher in the group of survivors homozygous or heterozygous variant for rs523349 (0.62 versus 0.57 mm, P = 0.026; 5.6 versus 3.1 mg/24 h, P = 0.017, respectively). No association was found between cardiometabolic status and SNP rs9282858 in SRD5A2.
  
  
  CONCLUSIONS
  Metabolic syndrome develops more frequently in testicular cancer survivors homozygous or heterozygous variant for SNP rs523349 in SRD5A2. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and vascular changes in testicular cancer survivors and is a target for intervention.
authors.affiliation: Medical Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Hink
authors.initials: H
authors.lastname: Boer
authors.affiliation: Medical Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Nico-Derk L
authors.initials: NL
authors.lastname: Westerink
authors.affiliation: Medical Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Renske
authors.initials: R
authors.lastname: Altena
authors.affiliation: Medical Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Janine
authors.initials: J
authors.lastname: Nuver
authors.affiliation: Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: D A Janneke
authors.initials: DAJ
authors.lastname: Dijck-Brouwer
authors.affiliation: Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: van Faassen
authors.affiliation: Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Klont
authors.affiliation: Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Ido P
authors.initials: IP
authors.lastname: Kema
authors.affiliation: Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Joop D
authors.initials: JD
authors.lastname: Lefrandt
authors.affiliation: Medical Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Nynke
authors.initials: N
authors.lastname: Zwart
authors.affiliation: Epidemiology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.affiliation: Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Smit
authors.affiliation: Medical Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Coby
authors.initials: C
authors.lastname: Meijer
authors.affiliation: Medical Oncology, University Medical Center Groningen, University of Groningen, The Netherlands. Electronic address: j.a.gietema@umcg.nl.
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001761:Bleomycin / Q000009:adverse effects; D002340:Carotid Artery Diseases / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D002945:Cisplatin / Q000009:adverse effects; D003430:Cross-Sectional Studies; D005047:Etoposide / Q000009:adverse effects; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D017741:Survivors; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D001761:Bleomycin; D013739:Testosterone; D005047:Etoposide; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human; D002945:Cisplatin
keywords: 3-Oxo-5-alpha-steroid 4-dehydrogenase; Albuminuria; Antineoplastic agents; Carotid intima-media thickness; Metabolic syndrome X; Single-nucleotide polymorphism; Survivors; Testicular neoplasms; Testosterone