Glutathione S-transferase T1, M1 and P1 gene polymorphisms and susceptibility to colorectal cancer, a Syrian population study

Abstract

Colorectal cancer (CRC) is considered to be the third most common cancer worldwide, and it is the fourth most common cause of cancer deaths. CRC is described as multifactorial disease. Among others, Glutathione S-transferases are known to act pro-carcinogenic in CRCs, however, they are needed for the conjugation between chemotherapeutics and a wide spectrum of xenobiotics. In this study, 70 patients with CRC and 85 healthy volunteers without any cancer history were genotyped. Polymorphism genotypes for the genes GSTP1, GSTT1 and GSTM1 were studied by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and/or multiplex polymerase chain reaction. Our finding showed a significant risk for CRC associated with GSTP1 heterozygous Ile/Val (OR = 1.8; 95% CI: 0.93–3.44; p = 0.009), while GSTP1 Val/Val homozygous was observed only in the CRC patients. Significant differences in the frequency of GSTM1- and GSTT1-null genotypes were found. The GSTT1-null genotype was higher in CRC group (34.3%) than in control group (12.9%) (OR = 3.5; 95% CI: 1.57–7.83; p = 0.001). The GSTM1-null was higher in CRC cases (42.8%) compared with control group (21.1%) (OR = 2.79; 95% CI: 1.38–5.64; p = 0.003).Individuals carrying combined, both GSTM1/GSTT1-null genotype, were associated with an estimated 7.56-fold higher risk to form CRC than those having GSTM1/GSTT1-present genotype. Individuals carrying combined three genotypes of GSTM1-null/GSTT1-null/ heterozygous Ile/Val genotype for GSTP1 were associated with an estimated 21.63-fold higher risk to be CRC than those carrying GSTM1-present/GSTT1-present/ Ile/Ile genotype of the GSTP1 (OR = 21.63; 95% CI: 2.39–195.82; p = 0.001). Also, individuals with combined three genotypes of GSTM1-null/GSTT1-present/ heterozygous Ile/Val genotype for GSTP1 were associated with an estimated 13.9-fold higher risk to be CRC than those carrying GSTM1-present/GSTT1-present/ Ile/Ile genotype of the GSTP1 (OR = 13.9; 95% CI: 2.60–74.35; p = 0.0007). Overall, the results of this pilot study in 70 patients revealed that the GSTM1-null genotype, alone or in combination with GSTT1-null genotype, GSTP1-heterozygous is associated with enhanced risk for CRC in Syrian population.