Molecular epidemiology of colon cancer

Colorectal cancer appears to have rapidly increased over the past two decades in Korea. Environmental factors, characterized by a western life style, seem to be closely related to the increased risk of colorectal cancer. Higher intakes of meat, a lower vegetable intake, a lack of physical activity, obesity, and alcohol drinking have been suggested to be risk factors for colorectal cancer in the numerous epidemiologic studies. Several specific associations have also been observed between genetic polymorphisms and colorectal cancer. Moreover, it has been postulated that environmental factors and a genetic predisposition work in concert in colorectal cancer development. A stronger association between red meat intake and colorectal cancer among those with rapid acetylators at either the NAT1 or NAT2 locus was reported, particularly for colorectal cancer associated with K-ras mutations. The protective effect of the homozygous variant TT form of the MTHFR genotype on the risk of colon cancer seems to be modified by the level of methyl diets, i.e., by folate, which has a protective effect, or conversely by alcohol. The insulin-related pathway, which possibly explains at a mechanistic level the effect of physical activity and obesity on colon cancer, appears to be a common denominator in colon cancer and in other metabolic disorders, such as diabetes mellitus and dyslipidemia. Hyperinsulinemia has been proposed as an explanation for the association between a Western lifestyle and colon cancer risk. Further studies, that incorporate both genetic and environmental factors, are needed to fully explain and identify the underlying pathway of colorectal carcinogenesis.