Association between polymorphisms in sex hormones synthesis and metabolism and prostate cancer aggressiveness
Metadatos
Mostrar el registro completo del ítemAutor
Robles Fernández, Inmaculada; Martínez González, Luis Javier; Pascual-Geler, Manrique; Cózar Olmo, José Manuel; Puche Sanz, Ignacio; Serrano Fernández, María José; Lorente Acosta, José Antonio; Álvarez Cubero, María JesúsEditorial
Plos One
Fecha
2017-10-05Referencia bibliográfica
Robles-Fernandez I, Martinez-Gonzalez LJ, Pascual-Geler M, Cozar JM, Puche-Sanz I, Serrano MJ, et al. (2017) Association between polymorphisms in sex hormones synthesis and metabolism and prostate cancer aggressiveness. PLoS ONE 12(10): e0185447. https://doi.org/10.1371/journal.pone.0185447
Resumen
Novel biomarkers for prostate cancer (PCa) diagnosis and prognosis are necessary to
improve the accuracy of current ones employed in clinic. We performed a retrospective
study between the association of several polymorphisms in the main genes involved in the
synthesis and metabolism of sex hormones and PCa risk and aggressiveness. A total of
311 Caucasian men (155 controls and 156 patients) were genotyped for 9 SNPs in AR,
CYP17A1, LHCGR, ESR1 and ESR2 genes. Diagnostic PSA serum levels, Gleason score,
tumor stage, D'Amico risk and data of clinical progression were obtained for patients at the
moment of the diagnosis and after 54 months of follow-up. Chi-squared test were used for
comparisons between clinical variables groups, logistic regression for clinical variables
associations between SNPs; and Kaplan±Meier for the association between SNPs and time
to biochemical progression. We found 5 variants (CYP17A1) rs743572, rs6162, rs6163;
(LHCGR) rs2293275 and (ESR2) rs1256049 that were statistically significant according to
clinical variables (PSA, D'Amico risk and T stage) on a case-case analysis. Moreover, the
presence of A and G alleles in rs743572 and rs6162 respectively, increase the risk of higher
PSA levels (>10 ng/μl). With respect to DÂAmico risk rs743572 (AG-GG), rs6162 (AG-AA)
and rs6163 (AC-AA) were associated with an increased risk; and last, AC and AA genotypes
for rs6163 were associated with a shorter biochemical recurrence free survival (BRFS)
in patients with radical prostatectomy. In multigene analysis, several variants in SNPs
rs2293275, rs6152, rs1062577, rs6162, rs6163, rs1256049 and rs1004467 were described
to be associated with a more aggressiveness in patients. However, none of the selected
SNPs show significant values between patients and controls. In conclusion, this study
identified inherited variants in genes CYP17A1, LHCGR and ESR2 related to more aggressiveness
and/or a poor progression of the disease. According to this study, new promise
PCa biomarkers for clinical management could be included in these previous SNPs.