Genetic polymorphisms of CYP2E1 and risk of colorectal adenomas in the Self Defense Forces Health Study.
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.
Morita
Makiko
M
Department of Preventive Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. mmorita@phealth.med.kyushu-u.ac.jp
Tabata
Shinji
S
Tajima
Osamu
O
Yin
Guang
G
Abe
Hiroshi
H
Kono
Suminori
S
D000236:Adenoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006306:Health Surveys; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008019:Life Style; D008297:Male; D008875:Middle Aged; D008889:Military Personnel / Q000706:statistics & numerical data*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors
D004273:DNA, Neoplasm; D019392:Cytochrome P-450 CYP2E1