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World J Gastroenterol. Nov 21, 2007; 13(43): 5725-5730
Published online Nov 21, 2007. doi: 10.3748/wjg.v13.i43.5725
CYP2E1 Rsa I polymorphism impacts on risk of colorectal cancer association with smoking and alcohol drinking
Chang-Ming Gao, Toshiro Takezaki, Jian-Zhong Wu, Min-Bin Chen, Yan-Ting Liu, Jian-Hua Ding, Haruhiko Sugimura, Jia Cao, Nobuyuki Hamajima, Kazuo Tajima
Chang-Ming Gao, Jian-Zhong Wu, Min-Bin Chen, Yan-Ting Liu, Jian-Hua Ding, Division of Epidemiology, Jiangsu Province Institute of Cancer Research, Nanjing 210009, Jiangsu Province, China
Toshiro Takezaki, Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
Haruhiko Sugimura, First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
Jia Cao, Molecular Toxicology Laboratory, Third Military Medical Universit School of Public Healthy, Chongqing 400038, China
Nobuyuki Hamajima, Department of Preventive Medicine Biostatistics and Medical Decision Making, Nagoya University School of Medicine, Nagoya 466-8550, Japan
Kazuo Tajima, Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
Author contributions: All authors contributed equally to the work.
Supported by a Grant-in Aid for International Scientific Research, Special Cancer Research, No.11137311, from the Ministry of Education, Science, Sports, Culture and Technology of Japan, and by a Major International (Regional) Joint Research Projects, No. 30320140461 from the National Natural Science Foundation of China
Correspondence to: Kazuo Tajima, Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan. ktajima@aichicc.jp
Telephone: +81-52-7642970 Fax: +81-52-7635233
Received: March 7, 2007
Revised: July 31, 2007
Accepted: September 16, 2007
Published online: November 21, 2007

AIM: 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).

CONCLUSION: 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.

Keywords: CYP2E1, Gene polymorphism, Smoking, Alcohol drinking, Colorectal cancer