CYP2E1 Rsa I polymorphism impacts on risk of colorectal cancer association with smoking and alcohol drinking.
OBJECTIVE
To investigate associations between the Rsa I polymorphism of CYP2E1 and risk of colorectal cancer.


METHODS
A case-control study was conducted with 315 colorectal cancer cases (105 colon, 210 rectal) and 439 population-based controls in Jiangsu Province of China. Genomic DNA samples were assayed for restriction fragment length polymorphisms in CYP2E1 by PCR amplification followed by digestion with Rsa I. Information on smoking and alcohol drinking was collected using a questionnaire. Odds ratios (ORs) were estimated with an unconditional logistic model.


RESULTS
The proportional distribution of the CYP2E1 Rsa I c1/c1, c1/c2 and c2/c2 genotypes were 61.4%, 35.6% and 3.0% in controls, 60.6%, 33.7% and 5.8% in colon cancer cases, and 58.4%, 34.0% and 7.7% in rectal cancer cases, respectively. A significant difference was noted between controls and rectal cancer cases (P = 0.029), the c2/c2 genotype being associated with elevated OR (adjusted age, sex and status of the smoking and alcohol drinking) for rectal cancer (1.64, 95% CI, 1.12-2.41, vs c1 allele carriers), but not for colon cancer. In interaction analysis between the CYP2E1 Rsa I genotype and smoking and drinking habits, we found a significant cooperative action between the c2/c2 genotype and alcohol drinking in the sex-, age-adjusted ORs for both colon (4.74, 95% CI, 1.10-20.40) and rectal (5.75, 95% CI, 1.65-20.05) cancers. Among non-smokers, the CYP2E1 Rsa I c2/c2 genotype was also associated with elevated ORs in the two sites (1.95, 95% CI, 0.99-3.86 and 2.30, 95% CI, 1.32-3.99).


CONCLUSIONS
The results of the present study suggest that the CYP2E1 c2/c2 genotype increases susceptibility to rectal cancer and the gene-environmental interactions between the CYP2E1 polymorphism and smoking or alcohol drinking exist for colorectal neoplasia in general.
Gao
Chang-Ming
CM
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
Takezaki
Toshiro
T
Wu
Jian-Zhong
JZ
Chen
Min-Bin
MB
Liu
Yan-Ting
YT
Ding
Jian-Hua
JH
Sugimura
Haruhiko
H
Cao
Jia
J
Hamajima
Nobuyuki
N
Tajima
Kazuo
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects*; D016022:Case-Control Studies; D002681:China; D015179:Colorectal Neoplasms / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
D019392:Cytochrome P-450 CYP2E1; D015252:Deoxyribonucleases, Type II Site-Specific; C040158:GTAC-specific type II deoxyribonucleases