Metabolic susceptibility genes and prostate cancer risk in a southern European population: the role of glutathione S-transferases GSTM1, GSTM3, and GSTT1 genetic polymorphisms

Prostate. 2004 Mar 1;58(4):414-20. doi: 10.1002/pros.10348.

Abstract

Background: Glutathione S-transferase (GST) metabolic enzymes may be involved in the development of human cancer. Genetic polymorphisms have been reported in GSTM1, GSTM3, and GSTT1 with functional alterations and influencing cancer risk.

Methods: We analyzed DNA samples from 335 (670 alleles) unrelated individuals, 185 community control subjects, and 150 prostate cancer (PC) patients, for GSTM1, GSTM3, and GSTT1 genotypes using polymerase chain reaction (PCR).

Results: The analysis of the frequencies from the 670 alleles indicates that men carrying two B-alleles (GSTM3) have increased risk for PC (OR = 5.50, 95% confidence interval (CI) 1.2-25.8; P = 0.016). Multivariate logistic regression analysis confirmed this association (OR = 5.2, 95% CI 1.1-25.0; P = 0.036). No increased PC risk was observed for men carrying any of the GSTM1 or GSTT1 genotypes (OR = 1.20, 95% CI 0.75-1.90; P = 0.420 for GSTM1 null and OR = 0.87, 95% CI 0.50-1.51; P = 0.550 for GSTM1 null). However, GSTT1 null was overrepresented in men with advanced PC disease (P = 0.038).

Conclusions: Our results indicate that polymorphism in the GSTM3 may be an important biomarker for PC risk, especially in the definition of the genetic risk profile of populations of southern Europe.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Confidence Intervals
  • DNA, Neoplasm / genetics
  • Europe / epidemiology
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Glutathione Transferase / genetics*
  • Humans
  • Male
  • Polymerase Chain Reaction / methods
  • Polymorphism, Genetic / genetics*
  • Portugal / epidemiology
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / genetics*
  • Reference Values
  • Risk Factors
  • Software
  • White People / genetics

Substances

  • DNA, Neoplasm
  • glutathione S-transferase T1
  • GSTM3 protein, human
  • Glutathione Transferase
  • glutathione S-transferase M1