Meat, metabolic genotypes and risk for colorectal cancer

Persuasive data exist as to the importance of environmental factors in the pathogenesis of sporadic colorectal cancer. One possibility is that the eff ect of environmental factors varies between individuals, perhaps on the bas is of inherited variation (polymorphism) in genes which influence the activ ation or inactivation of dietary carcinogens, Thus far, the focus has been on acetylator genes (NAT1, NAT2) and the activation of heterocyclic amines, carcinogens generated by cooking meat for prolonged periods at high temper ature. Three case-control studies and one prospective study have shown a co nsistent trend towards higher risks for cancer with higher intakes of meat in rapid acetylators for NAT1, NAT2 or both genotypes. Other links between meat, cooking methods, metabolic genotypes and risk for cancer might includ e enhanced activation of polycyclic aromatic hydrocarbons and N-nitroso com pounds by variant genotypes of CYP1A1 and CYP2E1, respectively, and modulat ion by meat of the protective effect of the epsilon 4 allele of apolipoprot ein E on risk for cancer of the proximal colon, (C) 1999 Lippincott William s & Wilkins.