Polymorphisms of biotransforming enzymes (GSTs) and their association with colorectal cancer in the Slovak population.

ABSTRACT

The aim of present study was to summarize the results of a case-control study focused on genetic polymorphisms of selected Phase II metabolizing enzymes (GSTM1, T1, P1) and to investigate the association of these polymorphisms with the colorectal cancer risk among the Slovak population. A case-control study with 183 colorectal cancer cases and 422 controls was conducted. DNA was extracted from peripheral blood leukocytes, and the polymorphisms of GSTM1, GSTT1 and GSTP1 enzymes were determined by PCR-based methods. Association between specific genotypes and the development of colorectal cancer were examined using logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTP1 val/val genotype (OR=2.1, 95%CI 1.1 - 4.0, chi2 = 0.28 and P = 0.0025) was associated with an elevated risk. The statistically significant correlation was found also for the combined genotypes of GSTM1 null and GSTP1 valine homozygosity (OR = 2.7, 95% CI 1.1-6.1, chi2 = 4.5 and P = 0.03). The genotype of certain metabolising enzymes affects the risk for colorectal cancer. This effect is also important when certain allelic combinations are studied. In the near future, individual risk assessment may be reached by further increasing the number of studies of polymorphisms, combining them with the traditional epidemiological risk factor.