Study of genetic predisposition in Egyptian colorectal cancer patients: role of phase II xenobiotic metabolizing genes polymorphism

ABSTRACT

The glutathione S-transferase [GST] supergene family is an important part of cellular enzyme defense against endogenous and exogenous chemicals, many of which have carcinogenic potential. The present investigation was conducted to evaluate the possible association between genetic polymorphisms of glutathione S-transferase M1 and T1 [GSTM1 and GSTT1], and susceptibility to colorectal cancer and the interaction with environmental factors. A case-control study of 50 patients and 50 healthy controls was conducted to investigate the role of GSTM1 and GSTT1 polymorphisms in colorectal cancer. Genotypes of GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction [PCR]. The frequencies of GSTM1 null and GSTT1 null genotypes in controls were 42% and 16%, respectively. The GSTM1 polymorphism was associated with an increased risk of developing colorectal cancer [p=0.002; OR=3.9, 95% CI 1.68- 9.15]. There was no significant association between GSTT1 null genotype and colorectal cancer risk. The GSTT1 deletions was associated with an increased risk of developing distal tumour [OR =5.25, 95% CI 1.6-16.7, p=0.006]. GSTM1 null genotype was significantly more common in patients who were diagnosed before the age of 40 years than in those who were diagnosed at an older age. This suggests that the GSTM1 genotype might influence the age of onset of colorectal cancer. In conclusion, the results of the present study suggest that GSTM1 null genotype and combined GSTM1/T1 null genotypes may confer a genetic susceptibility to colorectal cancer. In addition, other environmental factors such as smoking may also have a contributing role