Luis Alberto Henríquez-Hernández1, Almudena Valenciano2, Palmira Foro-Arnalot3, María Jesús Álvarez-Cubero4, José Manuel Cozar5, José Francisco Suárez-Novo6, Manel Castells-Esteve6, Pablo Fernández-Gonzalo7, Belén De-Paula-Carranza7, Montse Ferrer8, Ferrán Guedea9, Gemma Sancho-Pardo10, Jordi Craven-Bartle10, María José Ortiz-Gordillo11, Patricia Cabrera-Roldán11, Juan Ignacio Rodríguez-Melcón12, Estefanía Herrera-Ramos13, Carlos Rodríguez-Gallego14, Pedro C Lara15. 1. 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. 2. Instituto Canario de Investigación del Cáncer, Las Palmas, Spain. 3. Institud d׳Oncologia Radioteràpica, Hospital de la Esperanza, Parc de Salut Mar, Barcelona, Spain. 4. 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. 5. Department of Urology, Hospital Universitario Virgen de las Nieves, Granada, Spain. 6. Department of Urology, Hospital Universitari de Bellvitge, L׳Hospitalet de Llobregat, Spain. 7. Radiation Oncology Department, Onkologikoa, Guipuzcoa, Spain. 8. Health Services Research Group, Institut de Recerca Hospital del Mar (IMIM), Barcelona, Spain. 9. Department of Radiation Oncology, Institut Català d׳Oncologia (ICO), L׳Hospitalet de Llobregat, Spain. 10. Radiation Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 11. Radiation Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain. 12. Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain; Instituto Canario de Investigación del Cáncer, Las Palmas, Spain. 13. 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. 14. Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain. 15. 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.
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. PURPOSE: 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. PATIENTS AND 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.
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. PURPOSE: 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. PATIENTS AND 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: Prevathe Poniah; Zahurin Mohamed; Yamunah Devi Apalasamy; Shamsul Mohd Zain; Shanggar Kuppusamy; Azad Ha Razack Journal: Int J Clin Exp Med Date: 2015-10-15