Genetic polymorphisms and environmental factors in the etiology of colorectal caner

Environmental factors, including dietary and lifestyle factors, play an important role in the etiology of colorectal cancer. Advances in technology for gene analysis have generated many opportunities to elucidate genetic pathways of hereditary and sporadic colorectal cancer in the last decade. Highly penetrant mutations in certain genes, such as mismatch repair genes, play a major role in the development of hereditary colorectal cancer, while low penetrant polymorphisms play a role in metabolizing and DNA repair enzymes. Because these mutation are common, they may contribute to a large proportion of sporadic colorectal cancer. Since genetic polymorphisms may modulate an individual's response to DNA-damaging agents derived from the environment, evaluating the impact of these polymorphic genes and their interactions with environmental factors may enable us to identify susceptible subgroups and better characterize the etiology of sporadic colorectal cancer. In this review we summarize the current studies regarding the role of gene-environment interactions in the development of colorectal cancer, including genetic polymorphisms of metabolic enzymes (cytochrome P4501A1, cytochrome P4501A2, N-acetyltransferase and glutathione S-transferase) and DNA repair enzymes. We also briefly discussed areas of particular promise for further study and the limitations of these studies.