Association between Glutathione S-Transferase M1 and Ti Polymorphisms and Colorectal Cancer Risk in Patients from Kazakhstan

Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide and the incidence is increasing in developed as well as developing countries including Kazakhstan. Glutathione S-transferases (GSTs) are considered to be cancer susceptibility genes as they play a role in the detoxification of carcinogenic species. In this case-control study the influence of GSTMI and GSTTI polymorphisms on CRC risk in Kazakhstan population were evaluated. Methods: Blood samples were collected from patients diagnosed with rectal or colon cancer (300 individuals) as well as a control cohort of healthy volunteers (300 individuals), taking into account the age, gender, ethnicity, and smoking habits of the CRC patients. Deletion polymorphisms were genotyped employing a multiplex PCR amplification method. Association between polymorphisms and CRC susceptibility risk was calculated using multivariate analysis and logistic regression for odd ratio (OR). Results: The homozygous GSTMI null genotype was associated with significantly increased risk of CRC (OR = 2.01, 95% Cl = 1.45 - 2.79, p = 0.0001) while the homozygous GSST1 null genotype was not associated with the risk of developing CRC (OR = 1.10, 95% CI = 0.78 - 1.55, p = 0.001), but the heterozygous genotype correlated with CRC susceptibility (OR = 1.98, 95% CI = 1.30 - 3.00, p = 0.001). Also, separate analyses of each of the main ethnic groups (Kazakh and Russian) showed a strong association of GSTMI null genotype with CRC risk (for Kazakhs OR = 2.36, 95% Cl = 1.35- 4.10, p = 0.006 and for Russians OR = 1.84, 95% Cl = 1.17 - 2.89, p = 0.003). The CRC risk of GSTM1 null genotype in smokers was considerably higher (OR = 3.37, 95% Cl = 1.78 - 6.38, p = 0.0007). The combination of the GSTM1 and GSTTI null genotypes in combined mixed population of Kazakhstan showed a trend to increasing the risk of developing CRC (OR = 1.60, 95% CI = 1.00 - 2.56), but it was not statistically significant. Conclusions: In conclusion, the results of this case-control study for sporadic cases of CRC show that GSTMI deletion polymorphisms can have predictive value for susceptibility to CRC (OR = 2.01, p = 0.0001) for the mixed population from Kazakhstan and for both main ethnic groups (Kazakhs and Russians (OR = 2.36 and OR = 1.84, respectively)).