Cytochrome P450 2E1 Polymorphism in Gastric Cancer in Brazil: Case-Control Studies of Japanese Brazilians and Non-Japanese Brazilians

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 9; no. 7; pp. 675 - 680
• Main Authors: NOBUKO NISHIMOTO, I, HANAOKA, T, SUGIMURA, H, NAGURA, K, IHARA, M, LI, X.-J, ARAI, T, SHIGEAKI HAMADA, G, KOWALSKI, L. P, TSUGANE, S
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-07-2000
• Subjects: Aged; Biological and medical sciences; Brazil - epidemiology; Case-Control Studies; Cytochrome P-450 CYP2E1 - genetics; Diet; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Predisposition to Disease; Genotype; Humans; Japan - ethnology; Male; Medical sciences; Middle Aged; Polymorphism, Genetic; Risk Assessment; Stomach Neoplasms - ethnology; Stomach Neoplasms - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tropical medicine; Tumors; Brazil; Japan; Human; Stomach; Gene; Epidemiologic genetics; Cytochrome P450; Risk factor; Digestive diseases; Malignant tumor; Gastric disease; Polymorphism
• ISSN: 1055-9965; 1538-7755

Cytochrome P450 2E1 ( Cyp2E1 ) is involved in the
metabolic oxidation of carcinogenic nitroso compounds, including
N -nitrosoamines. There is an Rsa I
polymorphism in the transcriptional regulatory region of this gene, and
in vitro evidence suggests that the variant type of this
polymorphic site has higher 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 previous studies on
the relation between Cyp2E1 Rsa I
polymorphism and cancer susceptibility 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 Brazilians; 236 cases, 236 controls) in São Paulo
were designed to clarify the role of the Cyp2E1
Rsa I genotype in susceptibility to gastric cancer after
considering multifactorial environmental influences. The subjects with
variant Rsa I genotypes amounted to 47% (28 of 59) and
48% (64 of 133), respectively, of the Japanese cases and controls, and
6% (11 of 187) and 10% (19 of 192), respectively, of the non-Japanese
cases and controls. As expected, a difference in the distributions of
the two groups was observed. The odds ratio of the Rsa I
variant genotype of Cyp2E1 was 0.46 (95% confidence
interval, 0.21–1.04) in the non-Japanese Brazilian population and 0.98
(95% confidence interval, 0.50–1.90) in the Japanese Brazilian
population after adjusting for sex, age, tobacco use, and meat
consumption. Additional adjustment for potential confounding factors
did not change the odds ratio substantially. No significant
interactions were observed between the polymorphism and environmental
factors. In regard to the histological type of gastric cancer, the
variant genotype was significantly more prevalent than the common
genotype in Japanese subjects with diffuse type gastric cancer. Our
study suggests that the Cyp2E1 Rsa I
polymorphism is associated with a reduced risk of gastric cancer,
although how the assumed increase in Cyp2E1 expression
produced by this polymorphism is related to a reduced risk of cancer
remains unclear. The observations in this study are consistent with the
recent observations of esophageal cancer in endemic areas of China.