CYP2E1 RsaIpolymorphism impacts on risk of colorectal cancer association with smoking and alcohol drinking

Abstract

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 Ⅰc1/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 Ⅰgenotype 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 nonsmokers, the CYP2E1 Rsa Ⅰc2/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.

Relationship between growth hormone 1 genetic polymorphism and susceptibility to colorectal cancer

“…13,14 In this study, we found that the protective effect of the GH1 1663A/A genotype for colorectal cancer was more notable in nonsmokers of cigarettes and nondrinkers of alcohol. The relationship between GH1 and habitual smoking and drinking is unclear, but GH1 increases production of both IGF-1 and IGFBP-3, accounting in part for the relatively high correlation between plasma IGF-1 and IGFBP-3.…”

Polymorphisms of Alcohol Metabolizing Enzymes in Indigenous Mexican Population: Unusual High Frequency of CYP2E1*c2 Allele

“…2006; Gao et al, 2007;Hayashi et al, 1991;Lieber, 2004b;Ueno et al, 1996;Ueshima et al, 1996;Watanabe et al, 1994). The functional significance of this polymorphism may be due to its localization in the element response to the hepatic transcription factor HNF-1 (Hayashi et al, 1991).…”

Role and importance of polymorphisms with respect to DNA methylation for the expression of CYP2E1 enzyme

“…We set up the method previously described by Gao et al (2007) with some modifications developed in our laboratory. Briefly, PCR was performed using a final volume of 50 μl containing 150 ng of genomic DNA, 0.2 mM each dNTP, 1.5 mM MgCl 2 , 0.05 U/μl Taq polymerase (Invitrogen, USA) and 0.5 μM of each primer (5′-CCAGTCGAGTCTACAT TGTCA-3′sense and 5′-TTCATTCTGTCTTCTAACTGG-3′ anti-sense).…”