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 A and G alleles in rs743572 and rs6162 respectively, increase the risk of higher PSA levels (>10 ng/μl). With respect to D´Amico 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.
Highlights
Prostate cancer (PCa) is one of the most prevalent cancers diagnosed in men with 1.1 million cases worldwide in 2012 [1]
Nine SNPs across androgen receptor (AR), CYP17A1, luteinizing hormone chorionic gonadotropin hormone receptor (LHCGR), ESR1 and ESR2 genes were successfully genotyped in the total cohort (n = 311)
PCa is a hormone-dependent cancer; the androgen receptor (AR) axis plays a pivotal role in both disease development and progression [21]; for this reason we focused on PCa sex hormones related genes, to perform a retrospective study for the relation among AR, CYP17A1, LHCGR and ESR polymorphisms with PCa predisposition and severity
Summary
Prostate cancer (PCa) is one of the most prevalent cancers diagnosed in men with 1.1 million cases worldwide in 2012 [1]. One of the main challenges is to find new specific biomarkers that allow clinicians to detect the disease at an early stage, refine risk stratification, and control the course of patients. Only clinical risk classifications, such as that of DAmico [2], have gained enough evidence to be implemented in routine practice. A number of genomic classifications, such as FGFR1, CDKN1A and PMP22 genes [3], have demonstrated their ability to differentiate between low and high-risk patients [3,4,5], none of them are currently adopted in routine clinical practice [6]. There are not genetic biomarkers in the clinical to predict the outcome to different treatments used to attend PCa patients [7]
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