Gene-environment interaction involved in oral carcinogenesis: molecular epidemiological study for metabolic and DNA repair gene polymorphisms.
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AbstractBACKGROUND: Exposure to environmental carcinogens leads to oral squamous cell carcinoma (OSCC); however, the impact of genetic variations in carcinogen metabolisms and DNA repair on OSCC risk considering environmental exposures has not been clearly elucidated. METHODS: We conducted a case-control study with 122 cases and 241 controls. The risk of OSCC was evaluated in 10 genetic polymorphisms of nine genes, such as CYP1A1, CYP2E1, GSTM1, GSTT1, XPA, XPC, XPC, XPF and ERCC1. Gene-environment interaction was also evaluated. RESULTS: We found that CYP2E1 and XPA polymorphisms significantly affected the OSCC risk. Gene-environment interactions with smoking were significant for CYP2E1 and ERCC1 polymorphisms. Odds ratios for gene-environment interaction were 7.98 (P = 0.036), 9.67 (P = 0.017) and 8.49 (P = 0.031) for CYP2E1RsaI, DraI and ERCC1 polymorphisms, respectively. No interaction was observed with heavy drinking and any polymorphisms. CONCLUSION: CYP2E1, XPA and ERCC1 polymorphisms may affect the risk of OSCC.
CitationJ. Oral Pathol. Med. 2006, 35 (1):11-18
JournalJournal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
DescriptionBiomarkers of individual susceptibility: field studiesBiomarker (including alleles if genetic): CYP1A1 exon 7 (Ile462Val, A/G), CYP2E1 5Ά- (UTR; RsaI site), intron 6 (DraI site), XPA 5Ά-UTR (A23G) and XPG exon 15 (Asp1104His, C/G)Effect studied (phenotype/pathology): OSCC riskMethod of analysis: PCR, direct sequencingStudy design: case-controlStudy size: 122 cases, 241 controlsImpact on outcome (including dose-response): association of c2/c2 (CYP2E1*5B/*5B) genotypes of CYP2E1 5Ά-UTR (RsaI site) relative to the c1/c1 and c1/c2 (OR Ό 3.13, 95% CI: 1.15-8.52)CYP2E1*6/*6) genotype showed two times higher risk of OSCC compared with DD and DC subjects (OR Ό 2.36, 95% CI: 1.14-4.86)XPA 5Ά-UTR polymorphism showed significantly increased risk relative to AA (OR Ό 2.04, 95% CI: 1.18-3.55).(CYP1A1*2C/*2C) and AG genotypes showed reduced risk of OSCC relative to those with the AA (OR Ό 0.65, 95% CI: 0.40-1.04).ERCC1 3Ά-UTR with AA genotype showed 2-fold higher risk of OSCC compared to CC and CA subjects (OR Ό 1.95, 95% CI: 0.93-4.09).Lifestyle modulation of cancer & cancer biomarkersLifestyle element evaluated: smoking, alcoholOutcome studied (cancer or cancer biomarker): OSCC risk Method of biomarker analysis:PCR, direct sequencingStudy design (if human):case-controlStudy size (if human):122 cases, 241 controlsDose-response relationships observed: The impact of ever-smoking was 8-fold higher in those with CYP2E1 5Ά-UTR c1/c1 and c1/c2 subjects compared with c2/c2 subjects (P Ό 0.036).The impact of ever-smoking was 9-fold higher in those with DD and DC genotypes in CYP2E1 intron 6 polymorphisms relative to those with CC genotype (P Ό 0.017)ERCC1 polymorphism:Impact of smoking is 8-fold higher in those with CC and CA genotypes compared to those with the AA genotype (P Ό 0.031). KEYWORDS CLASSIFICATION: adverse effects;Alcohol Drinking;Biology;biomarkers of individual susceptibility: field studies;Carcinoma,Squamous Cell;Case-Control Studies;Cytochrome P-450 CYP1A1;Cytochrome P-450 CYP2E1;DNA-Binding Proteins;DNA Repair;etiology;Endonucleases;Environmental Exposure;Epidemiologic Studies;Epidemiology,Molecular;Female;genetics;Glutathione;Glutathione Transferase;Humans;Japan;Male;Middle Aged;Mouth Neoplasms;Polymorphism,Genetic;Proteins;Research;Risk Factors;Smoking;Transglutaminases;Xeroderma Pigmentosum;Xeroderma Pigmentosum Group A Protein;field studies;genetic;analysis.
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