Genetic polymorphisms of HNF1B, CASC17, CASC8 AND CCAT2 genes associated with prostate cancer risk in urologic patients

Polukonova N.V., Fomkin R.N., Pylaev T.E., Bucharskaya A.B., Mezirov G.G., Voronina E.S., Popkov V.M., Fomkina O.A., Krupinov G.E.

1) Research Institute of Fundamental and Clinical Uronephrology, urology department V.I. Razumovsky State Medical University of Saratov, Saratov, Russia; 2) Institute of Urology and Human Reproductive Health, Sechenov University, Moscow, Russia

Objective. The aim of the study was to analyze genomic combinations of four SNPs—rs4430796 (HNF1B), rs1859962 (CASC17), rs1447295 (CASC8), and rs6983267 (CCAT2) – associated with prostate cancer (PCa) in urological patients, including those with benign prostatic hyperplasia (BPH), PCa, and urolithiasis (UL). Materials and methods. A genetic study of blood samples from 236 patients in the Russian population was conducted, including 97 with benign prostatic hyperplasia (BPH), 89 with prostate cancer (PC) and 50 with urolithiasis (UL) – the control group. The extraction of DNA from venous blood was undertaken, and genotyping was subsequently performed by PCR followed by restriction degradation. Subsequently, the allele and genotype frequencies were compared between groups using the χ² test. Odds ratios (OR) and 95% confidence intervals were estimated. The results obtained from this study are as follows. An association was identified between mutant alleles T (HNF1B) and C (CASC17) in RP and BPH, which was absent in the control group. The TT genotype at rs4430796 (HNF1B) has been demonstrated to be associated with an increased risk of prostate cancer (OR=2,38; 95% CI: 1,26–4,47; p=0,004). The CC genotype at rs1859962 (CASC17) has also been demonstrated to be associated with prostate cancer (OR=3,80; 95% CI: 1,30–11,4; p=0,015). The TT (HNF1B) + CC (CASC17) combination was absent in patients with ICD, but was common in patients with RP and DGP. It is also considered a possible marker of the tumour process. The area under the curve (AUC) was 0,71, which corresponds to moderate diagnostic value. The genomic combinations GG TT (CASC8+CCAT2) and GG G/T exhibited differences between the DGP and RP groups. The study identified unique combinations of four single-nucleotide polymorphisms (SNPs) that are characteristic of patients with DGP. Conclusion. A combined analysis of polymorphisms rs4430796 and rs1859962 has the potential to serve as a basis for the genetic stratification of PR risk in the Russian population. The identified genomic combinations have potential as marker panels for screening and differentiation of PC and BPH, as well as for the development of personalised approaches in oncology.

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About the Authors

Corresponding author: R.N. Fomkin – Candidate of Medical Sciences, Associate Professor, Associate Professor of the Department of Urology, Senior Researcher, V.I. Razumovsky State Medical University of Saratov, Russian Ministry of Health, Research Institute of Fundamental and Clinical Uronephrology, Saratov, Russia; e-mail: rnfomkin@mail.ru

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