IS THE DEVELOPMENT OF ADENOMA AND CARCINOMA IN PROXIMAL COLON RELATEDTO APOLIPOPROTEIN-E PHENOTYPE

Background & Aims: Alterations in plasma lipoprotein levels and bile a cid metabolism observed in patients with colorectal adenoma and carcin oma may reflect a genetic background predisposing to altered lipid met abolism and tumors. This study was designed to determine whether the p olymorphism of apolipoprotein E, one of the key regulatory proteins in cholesterol metabolism, is associated with proximal or distal colonic neoplasia, Methods: Apolipoprotein E phenotype was determined in 135 patients with colorectal adenoma, 122 patients with colorectal carcino ma, and 199 randomly selected control subjects. Results: The frequency of the epsilon 4 allele of apolipoprotein E was low (0.075 and 0.073) in patients with proximal adenoma and those with carcinoma, respectiv ely, compared with the control subjects (0.181) (P < 0.05). In patient s with distal tumors, there was no alteration in epsilon 4 frequency, In all subjects with the epsilon 4 allele compared with subjects witho ut epsilon 4, the odds ratio for proximal adenoma was 0.36 (95% confid ence interval, 0.14-0.89), and the odds ratio for proximal carcinoma w as 0.35 (95% confidence interval, 0.14-0.86), Conclusions: The data su ggest that the epsilon 4 allele of apolipoprotein E provides protectio n from the development of adenoma and carcinoma of the proximal colon. These results support the theory that there are common susceptibility genes modulating the susceptibility to external carcinogenic factors.