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Title: Cigarette smoking, genetic polymorphisms, and colorectal cancer risk
Authors: Hoirun Nisa
Guan Yin
Suminori Kono
Keywords: Colorectal cancer;Cigarette smoking;gene-gene interaction;Case-control study;polymorphisms
Issue Date: 23-Jan-2009
Publisher: Japan Epidemiological Association
Series/Report no.: Supplement to Journal of Epidemiology;Vol. 19 No. 1
Abstract: Background: It is uncertain whether smoking is related to colorectal cancer risk whereas smoking has consistently associated with increased risk of colorectal adenomas. Different types of tobacco carcinogens are activated and detoxified through different metabolic pathways. Cytochrome P-450 (CYP)1A1, glutathione-S-transferase (GST), quinone oxidoreductase (NQO1) and epoxide hydrolase (EPHX1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known of these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the interaction between smoking and genetic polymorphism. Methods: The subjects were 685 cases of colorectal cancer and 778 community controls who gave informed consent to genetic analysis in the Fukuoka Colorectal Cancer Study, a population-based case control study. Lifestyle factors were ascertained by interview, and DNA was extracted from buffy coat. Genotyping was done for CYP1A1 6235T>A (MspI) and 4889A>G (Ile462Val), GSTM1, GSTT1, NQO1 609C>T (Pro187Ser) and EPHX1 Ex4+52A>G (His139Arg). Logistic regression analysis was used to control for sex, age, area, and other factors. Likelihood ratio test was used to assess the interaction. Results: Cigarette smoking was not associated with an increased risk of colorectal cancer. None of the individual polymorphisms under study was related to colorectal cancer risk and showed a measurable effect modification on the relation between smoking and colorectal cancer. Of the gene-gene interactions studied, GSTT1 and CYP1A1 Ile462Val polymorphisms showed a statistically significant interaction (P = 0.02). As compared with those having Ile/Ile genotype and GSTT1 non-null genotype, individuals with CYP1A1 462Val variant allele showed an odds ratio (OR) of 1.23 (95% CI: 0.90–1.69) when they had GSTT1 null genotype, and an OR of 0.76 (95% CI 0.56–1.01) when they had GSTT1 non-null genotype. The composite genotypes of these two polymorphisms, however, showed no measurable interaction with cigarette smoking in relation to colorectal cancer risk. Conclusion: The present study showed no clear association of cigarette smoking and genetic polymorphisms related to the metabolism of tobacco carcinogens with colorectal cancer risk. The observed interaction between GSTT1 and CYP1A1 Ile462Val polymorphisms may be a chance finding and needs further confirmation.
Description: Oral presentation in the 19th Japan Epidemiological Association Conference, 23-24 January 2009, Kanazawa, Japan
ISSN: 0917-5040
Appears in Collections:Prosiding Workshop/Lokakarya/Seminar

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