Abstract 883: Interaction between cigarette smoking and polymorphisms of xenobiotic-metabolizing genes on risk of oral premalignant lesions among male prisoners in Taiwan

Abstract

Abstract Background and Objective: The relationship between cigarette smoking and oral premalignant lesions has been previously demonstrated with strong epidemiological evidence. Glutathione S-transferases (GSTs) and cytochrome P450 1A1 (CYP1A1) and 2E1 (CYP2E1) are the key enzymes that metabolize cigarette smoking derived toxin and may be relevant to smoking-induced carcinogenesis. This case-control study was designed to examine whether polymorphisms of GSTM1, GSTT1, GSTP1, CYP 1A1, and CYP2E1 genes play roles in susceptibility to smoking-related oral premalignant lesions. Methods: We recruited participants who had undergone an oral screening from a penitentiary in Taiwan. Cases (n = 224) were prisoners who had more than 5 year imprisonment and confirmed oral premalignant lesions and controls were age and gender matched healthy prisoners (n = 492). Information about soci-demographic factors and smoking status were obtained by a self-administered questionnaire. Genotypes of GSTM1, GSTT1, GSTP1 Ile105Val, CYP1A1*2C* (A4889G), CYP2E1 Pst I (−1293G>C), and CYP2E1 Rsa I (−1053C>T) polymorphisms were determined by polymerase chain reaction or in combination with restriction fragment length polymorphism methods. Conditional logistic regressions were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Results: We found that the GSTM1 null genotype was more prevalent in cases than in controls (57.1 % vs. 49.4 %, p=0.054). After adjusting for BMI, cigarette smoking, alcohol drinking and betel nut chewing, the GSTM1 null genotype compared to the GSTM1 present genotype was moderately significantly associated with increased risk for oral premalignant lesions (OR = 1.36, 95% CI = 0.98-1.88), especially for leukoplakia (OR = 1.44, 95% CI = 1.00-2.07). This adverse effect was pronounced among smokers consuming cigarette ≫ 13 pack-years with ORs were 1.57 (95% CI = 0.99-2.46) and 1.62 (95% CI = 0.99-2.63), respectively. However, the interaction between GSTM1 genotype and cigarette use was not statistically significant. Similarly, comparing to the CYP1A1*2C A/G+G/G genotype, the CYP1A1*2C A/A genotype was more presented in all cases or leukoplakia (OR=1.36 and 1.65, respectively). The corresponding risk among heavy smokers were 1.69 (95% CI = 1.07-2.67) and 2.19 (95% CI = 1.31-3.65), respectively. There was no significant association between GSTT1, GSTP1 and CYP2E1 polymorphisms and risk of oral premalignant lesions. Conclusion: Our findings suggest that the GSTM1 null genotype and CYP1A1*2C A/A genotype may increase the risk of oral premalignant lesions, especially among heavy smokers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 883. doi:10.1158/1538-7445.AM2011-883