title: Genetic variations in genes involved in testosterone metabolism are associated with prostate cancer progression: A Spanish multicenter study.
abstract: BACKGROUND
  Prostate cancer (PCa) is an androgen-dependent disease. Nonetheless, the role of single nucleotide polymorphisms (SNPs) in genes encoding androgen metabolism remains an unexplored area.
  
  
  OBJECTIVE
  To investigate the role of germline variations in cytochrome P450 17A1 (CYP17A1) and steroid-5α-reductase, α-polypeptides 1 and 2 (SRD5A1 and SRD5A2) genes in PCa.
  
  
  METHODS
  In total, 494 consecutive Spanish patients diagnosed with nonmetastatic localized PCa were included in this multicenter study and were genotyped for 32 SNPs in SRD5A1, SRD5A2, and CYP17A1 genes using a Biotrove OpenArray NT Cycler. Clinical data were available. Genotypic and allelic frequencies, as well as haplotype analyses, were determined using the web-based environment SNPator. All additional statistical analyses comparing clinical data and SNPs were performed using PASW Statistics 15.
  
  
  RESULTS
  The call rate obtained (determined as the percentage of successful determinations) was 97.3% of detection. A total of 2 SNPs in SRD5A1-rs3822430 and rs1691053-were associated with prostate-specific antigen level at diagnosis. Moreover, G carriers for both SNPs were at higher risk of presenting initial prostate-specific antigen levels>20ng/ml (Exp(B) = 2.812, 95% CI: 1.397-5.657, P = 0.004) than those who are AA-AA carriers. Haplotype analyses showed that patients with PCa nonhomozygous for the haplotype GCTTGTAGTA were at an elevated risk of presenting bigger clinical tumor size (Exp(B) = 3.823, 95% CI: 1.280-11.416, P = 0.016), and higher Gleason score (Exp(B) = 2.808, 95% CI: 1.134-6.953, P = 0.026).
  
  
  CONCLUSIONS
  SNPs in SRD5A1 seem to affect the clinical characteristics of Spanish patients with PCa.
authors.affiliation: Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain; Instituto Canario de Investigación del Cáncer, Las Palmas, Spain; Clinical Sciences Department, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain. Electronic address: luis.henriquez@ulpgc.es.
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Henríquez-Hernández
authors.affiliation: Instituto Canario de Investigación del Cáncer, Las Palmas, Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Valenciano
authors.affiliation: Institud d׳Oncologia Radioteràpica, Hospital de la Esperanza, Parc de Salut Mar, Barcelona, Spain.
authors.forename: Palmira
authors.initials: P
authors.lastname: Foro-Arnalot
authors.affiliation: Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Facultad de Medicina, Universidad de Granada, Granada, Spain; GENYO, Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research, Granada, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Álvarez-Cubero
authors.affiliation: Department of Urology, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Cozar
authors.affiliation: Department of Urology, Hospital Universitari de Bellvitge, L׳Hospitalet de Llobregat, Spain.
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Suárez-Novo
authors.affiliation: Department of Urology, Hospital Universitari de Bellvitge, L׳Hospitalet de Llobregat, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Castells-Esteve
authors.affiliation: Radiation Oncology Department, Onkologikoa, Guipuzcoa, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Fernández-Gonzalo
authors.affiliation: Radiation Oncology Department, Onkologikoa, Guipuzcoa, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: De-Paula-Carranza
authors.affiliation: Health Services Research Group, Institut de Recerca Hospital del Mar (IMIM), Barcelona, Spain.
authors.forename: Montse
authors.initials: M
authors.lastname: Ferrer
authors.affiliation: Department of Radiation Oncology, Institut Català d׳Oncologia (ICO), L׳Hospitalet de Llobregat, Spain.
authors.forename: Ferrán
authors.initials: F
authors.lastname: Guedea
authors.affiliation: Radiation Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Sancho-Pardo
authors.affiliation: Radiation Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Craven-Bartle
authors.affiliation: Radiation Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Ortiz-Gordillo
authors.affiliation: Radiation Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cabrera-Roldán
authors.affiliation: Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain; Instituto Canario de Investigación del Cáncer, Las Palmas, Spain.
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Rodríguez-Melcón
authors.affiliation: Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain; Department of Medical and Surgical Sciences, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Herrera-Ramos
authors.affiliation: Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodríguez-Gallego
authors.affiliation: Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain; Instituto Canario de Investigación del Cáncer, Las Palmas, Spain; Clinical Sciences Department, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain.
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Lara
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D018450:Disease Progression; D005787:Gene Frequency; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D013030:Spain; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013739:Testosterone / Q000378:metabolism*; D044465:White People / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D013739:Testosterone; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548467:SRD5A1 protein, human; C548468:SRD5A2 protein, human; D017430:Prostate-Specific Antigen
keywords: CYP17A1; OpenArray; Prostate cancer; SNP; SRD5A1; SRD5A2