Genetic variations in UGT2B28, UGT2B17, UGT2B15 genes and the risk of prostate cancer: A case-control study

Gene. 2017 Nov 15;634:47-52. doi: 10.1016/j.gene.2017.08.038. Epub 2017 Sep 4.

Abstract

Glucuronidation is a major pathway for elimination of exogenous and endogenous compounds such as environmental carcinogens and androgens from the body. This biochemical pathway is mediated by enzymes called uridine diphosphoglucuronosyltransferases (UGTs). Null (del/del) genes polymorphisms in UGT2B17, and UGT2B28 and D85Y single-nucleotide polymorphism (SNP) of UGT2B15 have been reported to increase the risk of prostate cancer. The goal of this study was to determine the association of mentioned genetic variants with the risk of prostate cancer. We investigated the copy number variations (CNVs) of UGT2B17 and UGT2B28 loci and the association between rs1902023 polymorphism of UGT2B15 gene in 360 subjects consisted of 120 healthy controls, 120 prostate cancer (PC) patients and 120 benign prostatic hyperplasia (BPH) patients. No association was detected for the mentioned polymorphisms and the risk of PC. However, a significant association was detected between UGT2B17 copy number variation and BPH risk (OR=2.189; 95% CI, 1.303-3.675; p=0.003). Furthermore, we observed that the D85Y polymorphism increases the risk of BPH when analyzed in combination with the copy number variation of UGT2B17 gene (OR=0.135; 95% CI, 0.036-0.512; p=0.003). Our findings suggest that the D85Y polymorphism of UGT2B15 and CNVs in UGT2B28 and UGT2B17 genes is not associated with prostate cancer risk in Iranian patients. To our knowledge, this is the first report that implicates the role of CNV of UGT2B17 gene in BPH.

Keywords: Androgen; Benign prostatic hyperplasia; Copy number variation; Prostate cancer; Single-nucleotide polymorphism; UGT2B family.

MeSH terms

  • Aged
  • Case-Control Studies
  • DNA Copy Number Variations
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Glucuronosyltransferase / genetics*
  • Humans
  • Iran
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens / genetics*
  • Polymorphism, Single Nucleotide
  • Prostatic Hyperplasia / genetics*
  • Prostatic Neoplasms / genetics*

Substances

  • Minor Histocompatibility Antigens
  • UDP-glucuronosyltransferase, UGT2B28
  • Glucuronosyltransferase
  • UDP-glucuronosyltransferase 2B15, human
  • UGT2B17 protein, human
  • UGT2B28 protein, human