Cytochrome P450 2E1 polymorphism in gastric cancer in Brazil: Case-controlstudies of Japanese Brazilians and non-Japanese Brazilians

Cytochrome P450 2E1 (Cyp2E1) is involved in the metabolic oxidation of carc inogenic nitroso compounds, including N-nitrosoamines. There is an RsaI pol ymorphism in the transcriptional regulatory region of this gene, and in vit ro evidence suggests that the variant type of this polymorphic site has hig her transcriptional activity but less chlorzoxazone-metabolizing activity. Interindividual differences in the metabolic capacity of Cyp2E1 are assumed to be associated with cancer susceptibility, but the results of the previo us studies on the relation between Cyp2E1 RsaI polymorphism and cancer susc eptibility have been inconsistent. Two case-control studies of gastric cancer in Japanese Brazilians (96 cases , 192 controls) and Brazilians not of Japanese ancestry (non-Japanese Brazi lians; 236 cases, 236 controls) in Sao Paulo were designed to clarify the r ole of the Cyp2E1 RsaI genotype in susceptibility to gastric cancer after c onsidering multifactorial environmental influences. The subjects with varia nt RsaI genotypes amounted to 47% (28 of 59) and 48% (64 of 133), respectiv ely of the Japanese cases and controls, and 6% (11 of 187) and 10% (19 of 1 92), respectively, of the non-Japanese cases and controls. As expected, a d ifference in the distributions of the two groups was observed. The odds rat io of the RsaI variant genotype of Cyp2E1 was 0.46 (95% confidence interval , 0.21-1.04) in the non-Japanese Brazilian population and 0.98 (95% confide nce interval, 0.50-1.90) in the Japanese Brazilian population after adjusti ng for sex, age, tobacco use, and meat consumption. Additional adjustment f or potential confounding factors did not change the odds ratio substantiall y. No significant interactions were observed between the polymorphism and e nvironmental factors, In regard to the histological type of gastric cancer, the variant genotype was significantly more prevalent than the common geno type in Japanese subjects with diffuse type gastric cancer, Our study sugge sts that the Cyp2E1 RsaI polymorphism is associated with a reduced risk of gastric cancer, although how the assumed increase in Cyp2E1 expression prod uced by this polymorphism is related to a reduced risk of cancer remains un clear. The observations in this study are consistent with the recent observ ations of esophageal cancer in endemic areas of China.