乙醯轉移酵素之基因NAT1、NAT2多型性、吸菸、喝酒及嚼食檳榔與口腔癌癌前病變之關聯

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Title:	乙醯轉移酵素之基因NAT1、NAT2多型性、吸菸、喝酒及嚼食檳榔與口腔癌癌前病變之關聯 The association between polymorphisms of N-acetyltransferase genes NAT1, NAT2, cigarette smoking, alcohol consumption, betel chewing and oral precancerous conditions
Authors:	蔡瑋琪
Contributors:	公共衛生學系碩士班
Keywords:	口腔癌癌前病變、乙醯轉移酵素、監獄 oral precancerous lesions, N-acetyltransferase, prison
Date:	2011-07-27
Issue Date:	2011-10-17 16:16:06 (UTC+8)
Publisher:	中國醫藥大學
Abstract:	背景：近五年，臺灣口腔癌發生率及死亡率增加快速。對男性而言，口腔癌是發生率高且發生年齡早的癌症，因此若能早期發現口腔癌癌前病變的徵兆並早期治療或密切觀察，則對國人健康及國家的經濟發展助益甚大。而目前已有研究指出菸、酒及檳榔的暴露與罹患口腔癌及癌前病變的風險有關。當這些環境暴露產生的有害物質，特別是在吸菸過程所產生的芳香族胺（aromatic amines）等致癌物質進入體內後，個體可透過乙醯轉移酵素之活化及去活化的作用機轉來調節；然而在相同暴露下，個體對疾病的易感受性也隨之不同，此差異可能與基因的多型性或單倍體有關。目標：本研究探討代謝基因NAT1（rs4986990 G>A、rs15561 A >C）、NAT2 （rs1041983 C>T codon 94、rs1799930 G>A codon 197、rs1799931 G>A codon 286) 基因多型性及單倍體（haplotype）、基因與環境暴露因子間或基因與基因間之交互作用對口腔癌癌前病變之影響，另亦計算攜帶之環境暴露因子個數及風險對偶基因個數與罹患口腔癌癌前病變之風險。方法：本研究使用配對病例對照研究（matched case-control study）。研究對象來自臺中監獄成年男性收容人，收樣時間自2007年10月至2009年5月，經由耳鼻喉科醫師進行口腔健康檢查，若診斷為紅斑、白斑、疣狀增生及口腔黏膜纖維化等口腔癌癌前病變情況者視為病例組，對照組則從口腔黏膜健康者中挑選出與病例組年齡組頻率配對之個案，而年齡組的組距是5歲（病例組:對照組=1:4）。統計分析主要使用邏輯斯迴歸（logistic regression）分析，評估NAT1、NAT2基因多型性、單倍體、攜帶環境暴露因子個數及風險對偶基因與口腔癌前病變之關聯性。結果：校正人口學變項及暴露因子後，發現攜帶NAT2風險對偶基因之趨勢效應有達統計水準（p = 0.0475）；另將NAT1及NAT2風險對偶基因一起考慮時，發現風險對偶基因趨勢效應是顯著的（p = 0.0092）。在單倍體分析中，發現攜帶rs4986990 G -rs15561 C - rs1041983 T - rs1799930 G -rs1799931 A 單倍體可能會顯著提高罹病風險（校正後勝算比為2.05，95% 信賴區間=1.09-3.85）。結論：從結果顯示研究對象所攜帶之吸菸、喝烈酒及嚼食檳榔習慣個數、NAT1、NAT2風險對偶基因或單倍體皆可能與罹患口腔癌癌前病變有關。 Background : The incidence and mortality of oral cancer have increased quickly in the past five years in Taiwan. For men, oral cancer not only occurs at high incidence but also occurs at an early age. Therefore, if we can detect the oral precancerous conditions early and receive the treatment in time or follow up intensively, then it would be of great help on people’s health and the development of our country's economy. Some studies have been reported that the association between cigarette smoking, alcohol consumption, betel chewing and the risk of oral cancer and precancerous conditions. When people are exposed to harmful substances, especially aromatic amines and other carcinogenic substances, thses substances will be regulated by N-acetyltransferase (NAT) through activation or detoxication of the carcinogenic metabolic pathway. However, the individual susceptibility to disease at the same exposure is different, the difference may be due to the effect of gene polymorphisms and haplotypes. Aim : The aim of the present study was to investigate the association between oral precancerous conditions and xenobiotic metabolizing gene NAT1(rs4986990 G>A、rs15561 A >C)、NAT2 (rs1041983 C>T codon 94、rs1799930 G>A codon 197、rs1799931 G>A codon 286) polymorphisms and haplotypes,and to evaluate the gene-gene and gene-environment interactions in oral precancerous conditions. Methods : We conducted a matched case-control study and the participants in present study were adult males who were enrolled from October 2007 to May 2009. All of participants were examined by otolaryngologist, if participants were diagnosed as the oral precancerous conditions like leukoplakia, erythroplakia, verrucous hyperplasia and oral submucous fibrosis were cases in the study and the others without any oral precancerous conditions and oral cancer were selected by 4 (controls):1 (case) frequency matching with the cases in the same 5-yr age group. The main effects of genetic and environmental factors, the gene-gene and gene-environment interactions on oral precancerous conditions were estimated by logistic regression. Results : After adjusting for demographic and environmental factors, we found that the trend effect of individual carrying NAT2 risk alleles has reached the statistical significance (p = 0.0475); and the trend effect of the combination of NAT1 and NAT2 risk alleles for oral precancerous conditions was significant (p=0.0092). In the haplotype analysis, individuals carrying an rs4986990 G -rs15561 C - rs1041983 T - rs1799930 G-rs1799931 A haplotype were at a significantly increased risk of oral precancerous conditions (adjusted odds ratio (OR) =2.05, 95% Confidence Interval (CI) =1.09-3.85). Conclusions: Our results suggest that the number of environmental exposure factor or carrying NAT1 and NAT2 risk alleles may be associated with oral precancerous lesions.
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