Molecular evaluation of glutathione S transferase family genes in patients with sporadic colorectal cancer.

Aim: To evaluate the association between polymorphisms in glutathione S transferases (GSTs) and the risk of sporadic colorectal cancer (SCRC), tumor progression and the survival of patients.

Methods: A case-control study of 970 individuals from the Brazilian population was conducted (232 individuals from the case group with colorectal cancer and 738 individuals from the control group without a history of cancer). PCR multiplex and PCR-RFLP techniques were used to genotype the GST polymorphisms. The tumors were categorized according to the TNM classification: tumor extension (T), affected lymph nodes (N), and presence of metastasis (M). Logistic regression, multiple logistic regression and survival analysis were used to analyze the data. The results are presented in terms of odds ratio (OR) and 95% confidence interval (CI). The level of significance was set at 5% ( ≤ 0.05).

Results: Age equal to or over 62 years (OR = 8.79; 95%CI: 5.90-13.09, < 0.01) and female gender (OR = 2.91; 95%CI: 1.74-4.37; < 0.01) were associated with increased risk of SCRC. Analysis of the polymorphisms revealed an association between the polymorphisms and a risk of SCRC (OR = 1.45; 95%CI: 1.06-2.00; = 0.02), as well as between and a reduced risk of the disease (OR = 0.65; 95%CI: 0.43-0.98; = 0.04). An interaction between the presence of the wild-type allele of Ile105Val polymorphism and tobacco consumption on risk of SCRC (OR = 2.33; 95%CI: 1.34-4.05; = 0.05) was observed. There was an association between the null genotype and the presence of advanced tumors (OR = 2.33; 95%CI: 1.23-4.41; = 0.009), as well as increased risk of SCRC in the presence of a combination of non-null/ null genotypes (OR = 1.50; 95%CI: 1.03-2.19; = 0.03) and non-null/ null/ Val* (OR = 1.85; 95%CI: 1.01-3.36, = 0.04). Combined non-null/ null genotypes (OR = 2.40; 95%CI: 1.19-4.85; = 0.01) and non-null/ null/ Val* (OR = 2.92; 95%CI: 1.05-8.12; = 0.04) were associated with tumor progression. Polymorphisms were not associated with the survival of patients with SCRC.

Conclusion: Females aged 62 years or older are more susceptible to SCRC. Polymorphisms of and null genotypes modulated the susceptibility to SCRC in the population studied.