Genetic polymorphisms in xenobiotic-metabolizing enzymes and their association with colorectal cancer

Background: Carcinogenesis is a complex process associated with genetic and lifestyle factors. One of the most common forms of cancer is colorectal cancer (CRC). CRC affects approximately 5% of worldwide population. More than 75% of CRC cases represent sporadic forms. Susceptibility to nonhereditary CRC is significantly influenced by polymorphisms and mutations in low-penetrance genes. Genetic polymorphisms in xenobiotic-metabolizing enzymes may result in variations in detoxification capacity and thus influence the levels of carcinogenic compounds and subsequently the risk of cancer. Therefore, we aimed to study associations of polymorphisms in genes coding biotransformation enzymes with CRC. Based on frequency in Czech population and functional effects we selected polymorphisms in CYP1B1, EPHX1, GSTM1, GSTT1, GSTP1, NQO1 and SOD2.
Materials and Methods: Through the PCR RFLP and DNA sequencing analysis we followed their prevalence in groups of 500 CRC patients and 500 controls.
Results: Statistical analysis showed:

1. the lack of association of particular polymorphisms with CRC risk in unselected population
2. Female carriers of variant genotype in NQO1 were at significantly higher risk of CRC in comparison with those carrying normal genotype. There was no association of this polymorphism with CRC risk in males, but previously we reported its role in breast cancer in Czech and Austrian populations.
3. Age played no role as confounding factor.

Conclusions: First study of this kind on Czech population showed that polymorphisms in xenobiotic-metabolizing enzymes may present risk factors in CRC. Further study should be focused at searching for differences in exposure between genders and assessment of importance of polymorphism combinations. Identified risk modifying factors may be used for formulation of preventive and therapeutic strategies.
This project was supported by grants of the Grant Agency of the Czech Republic, grant no.: 310/05/2626 and Internal Grant Agency of Czech Ministry of Health, grant no.: 8563-5.