DNA修補基因的多型性與口腔癌癌前病變之關聯

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题名:	DNA修補基因的多型性與口腔癌癌前病變之關聯 The Association of DNA Repair Gene Polymorphisms with Oral Precancerous Lesions and Conditions
作者:	王昱蒼
贡献者:	公共衛生學系碩士班
关键词:	白斑;紅斑;黏膜纖維化;口腔癌 leukoplakia;erythroplakia;submucous fibrosis;oral cancer
日期:	2011-07-27
上传时间:	2011-10-17 16:16:03 (UTC+8)
出版者:	中國醫藥大學
摘要:	背景:根據國民健康局與行政院衛生署的資料，指出男性口腔癌的發生率與死亡率皆為十大癌症的第四名，對男性的影響深遠。雖然口腔癌癌前病變對健康的影響看似不大，實際上各種口腔癌癌前病變皆可能經由惡性轉變導致口腔癌。而DNA單一個核苷酸多型性(SNP)可能會改變DNA修補酵素的結構和修復的能力，若DNA修補機制發生缺陷則可能引起多種癌症。目的:探討XRCC1(rs1799782, rs25487, and rs25489)、XRCC3(rs861539 and rs1799796)與ERCC2(rs13181, rs238406, and rs1799793)基因型/單倍體與口腔癌癌前病變之關聯以及基因環境間的交互作用。方法:自2007年10月到2009年5月收取台中監獄成年男性收容人為樣本，受試者皆經由耳鼻喉科醫師進行口腔篩檢，若被診斷為白斑、紅斑、扁平苔癬、疣狀增生或口腔黏膜纖維化者即為病例組，對照組則是無任何口腔癌癌前病變或癌症並且經由與病例年齡(組距為5歲)頻率配對所選取而得。病例與對照皆於簽署同意書後填寫問卷並提供血液檢體以進行8個SNPs的基因型鑑定。以非條件式羅吉斯迴歸(unconditional logistic regression)估算勝算比(odds ratio)與95%信賴區間。結果:以XRCC1 rs1799782 GG+AG基因型為參考組，受試者帶有AA基因型者其罹患口腔癌癌前病變的風險會顯著的提高1.75倍(95% CI =1.01-3.04)。相較XRCC1單倍體為rs25487 G-rs25489 A-rs1799782 G/G-A-G者，攜帶A-G-G/G-A-G單倍體者，其校正潛在的干擾因子後罹病風險會增加1.60倍(95% CI =0.99-2.58)。若攜帶單倍體為ERCC2 rs13181 G-rs1799793 A-rs238406 G/T-G-T則比帶有單倍體為T-G-T/T-G-T者易於罹病(OR=2.14, 95% CI =1.01-3.04)。以3個XRCC1 SNPs未帶有任何危險基因型者為基準，帶有1種或2種危險基因型其校正後勝算比依序為1.43(95% CI =0.88-2.32)、1.93 (95% CI =1.05-3.54)，並且有顯著的趨勢效應(p=0.0330)。與ERCC2 3個SNPs未帶有任何危險基因型者相比，同時擁有3個危險基因型者會顯著的增加3.20倍(95% CI =1.09-9.38)的罹病風險。研究中未發現基因與環境間存在顯著的交互作用。結論:由本研究結果得知XRCC1與ERCC2的基因多型性與單倍體在罹患口腔癌癌前病變的過程之中可能扮演著一個重要的角色。 INTRODUCTION: According to the Department of Health, Executive Yuan, R.O.C. and the Bureau Health Promotion, Department of Health, R.O.C. (TAIWAN), oral cancer in men was the fourth leading cause of death from cancer and the fourth high incidence among cancers. Although oral precancerous lesions and conditions (OPLC) may not harmful to health, it could result in malignant transformation to oral cancer. DNA single nucleotide polymorphisms (SNPs) may alter structures of the DNA repair enzyme and the capacity of repair. The defects of DNA repair mechanisms may cause a variety of cancer. PURPOSE: The aims of the study were to assess the association between XRCC1 (rs1799782, rs25487, and rs25489), XRCC3 (rs861539 and rs1799796), ERCC2 (rs13181, rs238406, and rs1799793) genotypes/haplotypes and oral precancerous lesions, and to acessess the interaction of genetic and environmental factors. METHODS: The target population was male inmates in Taichung Prison. We recruited cases and controls during the period of Oct 2007 to May 2009. Cases were defined as those in whom any oral precancerous lesion including erythema, leukoplakia, lichen planus, or verrucous hyperplasia diagnosed by an otorhinolaryngist. Controls had no any precancerous lesions and were matched with cases on the 5-year age group. All subjects completed a questionnairewith an informed consent and provided blood samples for genotyping 8 SNPs. Unconditional logistic regression was used for calculating odds ratio and 95% confidence interval. RESULTS: With XRCC1 rs1799782 GG+AG genotypes as the reference group, carrying an AA genotype was assocaitd with an elevated risk (the adjusted odds ratio (OR) was 1.75 and 95% confidence interval (CI) was 1.01-3.04). Compared with the men who has two XRCC1 rs25487 G-rs25489 A-rs1799782 G haplotypes, carryingA-G-G/G-A-G haplotypes increased the risk of OPLC (OR=1.60, 95% CI =0.99-2.58). We found that ERCC2 rs13181 G-rs1799793 A-rs238406 G/T-G-G haplotypes has an excess risk than T-G-T/T-G-T haplotypes (OR=2.14 and 95% CI =1.01-3.04). As the number of the risk genotypes of XRCC1 increased, the risk of OPLC also elevated (p value for trend=0.0330). The risk among men had three risk genotypes of ERCC2 siginificantly enhanced about three times (95% CI =1.09-9.38) higher than whom with no risk genotypes. There was no significant interaction between genes and environmental exposures observed in the present study. CONCLUSION: The polymorphisms/haplotypes of XRCC1 and ERCC2 may play an important role in developing OPLC.
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