Interactions between Cigarette Smoking and Polymorphisms of Xenobiotic-Metabolizing Genes: The Risk of Oral Leukoplakia

Yu-Fen Li,Fung-Chang Sung,Chun-Hung Hua,Chiu-Shong Liu,Yao-Te Huang,Ming-Hsui Tsai,Chih-Ching Yeh

doi:10.1155/2013/983568

Abstract

Background: This case-control study investigates the role of xenobiotic-metabolizing genes, including glutathione S-transferases (GSTs) and cytochrome P450 1A1 (CYP1A1) and 2E1 (CYP2E1), in the susceptibility to oral potentially malignant disorders (OPMDs).Methods: The genotypes of GSTM1, GSTT1, GSTP1, CYP1A1∗2C, and CYP2E1 PstI/RsaI polymorphisms were determined for 217 OPMD cases and 492 age- and sex-matched controls from a Taiwanese penitentiary.Results: Compared to the GSTM1-present genotype, the GSTM1-null genotype was significantly associated with increased risk of leukoplakia (odds ratio [OR]=1.46, 95% l [CI]=1.01–2.10). Similarly, compared to the CYP1A1∗2C A/G+G/G genotype, the CYP1A1∗2C A/A genotype was significantly associated with increased risk of leukoplakia (OR=1.64, 95% CI=1.12–2.40), particularly for smokers consuming > 13 pack-years of cigarettes (OR=2.40, 95% CI=1.40–4.11) (Interaction P=0.039). In addition, participants with 4–5 risk genotypes (OR > 1) experienced higher risks for leukoplakia than those with 0-1 risk genotypes (OR=3.19, 95% CI=1.65–6.15) (Trend test P=0.001).Conclusions: Our findings suggest that the CYP1A1∗2C A/A genotype may increase the risk of leukoplakia, especially for heavy smokers. Xenobiotic-metabolizing genes may simultaneously modulate this disease risk. These observations require further confirmation with larger samples.

Highlights

Oral cancer is one of most commonly diagnosed cancers, with an estimated 263,900 new cases and 128,000 deaths from this disease occurring in 2008worldwide
This is the first case-control study with a relatively large sample to simultaneously investigate the association among 5 polymorphisms of xenobioticmetabolizing genes and oral potentially malignant disorders (OPMDs) risk in a male ethnic Chinese (i.e., Taiwanese) population in Taiwan
Results showed that the GSTM1-null and cytochrome P450 1A1 (CYP1A1)*2C A/A genotypes were positively associated with a risk of OPMDs, leukoplakia

Summary

Introduction

Oral cancer is one of most commonly diagnosed cancers, with an estimated 263,900 new cases and 128,000 deaths from this disease occurring in 2008worldwide. In Taiwan, oral cancer is the fourth leading cause of cancer death in men and is the most common cancer in people aged 24–45 years [2]. The age-standardized mortality rate for oral cancer in Taiwan was 15.2 per 100,000 people in 2011, which is substantially higher than in other countries. Li et al / Cigarette smoking, and polymorphisms of xenobiotic-metabolizing genes and risk of oral leukoplakia. Compared to the CYP1A1*2C A/G+G/G genotype, the CYP1A1*2C A/A genotype was significantly associated with increased risk of leukoplakia (OR = 1.64, 95% CI = 1.12–2.40), for smokers consuming > 13 pack-years of cigarettes (OR = 2.40, 95% CI = 1.40–4.11) (Interaction P = 0.039). Xenobiotic-metabolizing genes may simultaneously modulate this disease risk These observations require further confirmation with larger samples

Methods

Results

Conclusion