Association between polymorphisms in sex hormones synthesis and metabolism and prostate cancer aggressiveness

Abstract

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 and alleles in rs743572 and rs6162 respectively, increase the risk of higher PSA levels (>10 ng/μl). With respect to D´Amico risk rs743572 (), rs6162 () and rs6163 () were associated with an increased risk; and last, and 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.

The impact of transcription on metabolism in prostate and breast cancers

“…acetate, an inhibitor of 17α-hydroxylase and C17,20 lyase (CYP17A1) for the treatment of men with advanced CRPC (Ryan et al 2013). In fact, genetic polymorphisms of CYP17A1 are associated with higher aggressiveness and risk of progression to CRPC in patients receiving androgen deprivation therapy (Robles-Fernandez et al 2017). The importance of cholesterol in PCa progression is further established by a clinical study by Platz et al where the use of statins (cholesterol-lowering drugs) in patients is found to be associated with reduced risk of metastatic PCa (Platz et al 2006).…”

Exploring Prostate Cancer Patients’ Interest and Preferences for Receiving Genetic Risk Information About Cancer Aggressiveness

“…Using this information, patients can be stratified by risk to better determine the appropriate treatment. A number of studies reported that SNPs in genes such as AKT3 (minor allele frequency or MAF of 0.18), CYP17A1 (0.40), LHCGR (0.49), ESR2 (0.03), PRKCQ (0.15), HIF1A (0.04), MMP16 (0.12), and EGFR (0.39) may be biomarkers for aggressive cases (Fraga et al, 2014;Lavender et al, 2012;Lin et al, 2013;Robles-Fernandez et al, 2017). However, as already mentioned, these SNPs appear to have limited clinical value for prognosis.…”

Association between estrogen receptor β polymorphisms and prostate cancer in a Slovak population

“…In the present study, there was no association between the rs4986938 and rs1256049 polymorphisms and the risk of prostate cancer development and progression. The majority of published studies have also not confirmed an association between the rs4986938 and rs1256049 polymorphisms in the Caucasian population (40)(41)(42)(43)(44) or in mixed populations (45)(46)(47) and prostate cancer risk. On contrary, there are some studies that have described a significant association between the rs4986938 and rs1256049 polymorphisms and increased risk of prostate cancer development in Iranian (48) and Caucasian populations (49).…”