Genetic polymorphisms of CYP2E1 and risk of colorectal adenomas in the Self Defense Forces Health Study.

Abstract

CYP2E1 is an enzyme involved in the metabolism of N-nitrosamines and other carcinogenic substances. Functional RsaI and 96-bp insertion polymorphisms in 5'-flanking region have drawn interest in relation to the risk of colorectal cancer. We investigated the relation of these genetic polymorphisms and colorectal adenoma, a well-established precursor lesion of colorectal cancer. Subjects were 455 cases of colorectal adenomas and 1,052 controls of normal colonoscopy among men receiving a preretirement health examination in the Self Defense Forces. Genotypes were determined by either PCR-RFLP or PCR method. Statistical adjustment was made for smoking, alcohol use, body mass index, physical activity, and others. Individuals with RsaI c2 allele showed a decreased risk of proximal colon adenomas; adjusted odds ratios (95% confidence interval) of proximal and distal adenomas for the c1/c2 or c2/c2 genotype versus c1/c1 was 0.61 (0.41-0.88) and 0.95 (0.71-1.27), respectively. CYP2E1 96-bp insertion allele was associated with an increased risk of large (> or = 5 mm) adenomas; adjusted odds ratios (95% confidence interval) of large and small adenomas for having at least one insertion allele were 1.41 (1.03-1.94) and 0.94 (0.71-1.25), respectively. A suggestive effect modification was noted for alcohol consumption on the association between RsaI polymorphism and proximal adenomas (P(interaction) = 0.09) as well as on the association between 96-bp insertion and large adenomas (P(interaction) = 0.05). These findings indicate that variation in activity and inducibility of CYP2E1 contribute to the development of colorectal carcinogenesis.

• Authors: Makiko Morita, Shinji Tabata, Osamu Tajima, Guang Yin, Hiroshi Abe, Suminori Kono
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 17 Issue 7 Pg. 1800-7 (Jul 2008) ISSN: 1055-9965 [Print] United States
• PMID: 18628434 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Neoplasm
• Cytochrome P-450 CYP2E1

Topics

• Adenoma (diagnosis, epidemiology, genetics)
• Alleles
• Colonoscopy
• Colorectal Neoplasms (diagnosis, epidemiology, genetics)
• Cytochrome P-450 CYP2E1 (genetics)
• DNA, Neoplasm (genetics)
• Follow-Up Studies
• Genetic Predisposition to Disease
• Genotype
• Health Surveys
• Humans
• Incidence
• Japan (epidemiology)
• Life Style
• Male
• Middle Aged
• Military Personnel (statistics & numerical data)
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Retrospective Studies
• Risk Factors