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| Title: | 抽菸、綠茶飲用與DNA甲基轉移? (DNMT) 3B基因多形性對於DNA傷害與肺癌發生之效應
Effects of smoking, green tea consumption, and DNA methylatransferase 3B genetic polymorphism on DNA damage and lung cancer |
| Authors: | 黃家禎
Huang, Chia-Chen |
| Contributors: | 中山醫學大學;健康管理學院;公共衛生學系碩士班;李鴻森;翁瑞宏 |
| Keywords: | 肺癌;抽菸;綠茶飲用;DNMT3B基因型;DNA傷害
lung cancer;smoking;green tea consumption;DNMT3B genotype;DNA damage |
| Date: | 2012 |
| Issue Date: | 2012-12-21T06:41:53Z (UTC)
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| Abstract: | 肺癌 (lung cancer)，是世界各地的主要癌症之一。抽菸會導致DNA甲基化 (methylation) 穩定性增加，進而促使腫瘤抑制基因 (tumor suppressor gene) 過度甲基化，並且對於致癌物呈現出敏感性，因而容易引起DNA損傷。而DNA甲基轉移? (DNA methyltransferase [DNMT]) 3B為DNA甲基轉移?家族成員；特別的是，抗氧化劑茶多酚 (tea polyphenols) 可能能夠抑制DNA甲基轉移?的活性，進而降低腫瘤的發生。因此，我們設計一項病例對照研究來評估抽菸、綠茶飲用和DNMT3B -149 基因多形性對於DNA傷害與肺癌發生危險的效應。總計，有190名原發性肺癌病例與380名對照被納入本研究，以問卷收集人口學特徵、抽菸習慣、綠茶飲用、蔬果攝取、烹飪情況以及肺癌家族史。DNMT3B -149 基因型是以聚合?鏈鎖反應 (polymerase chain reaction) 加以辨識，細胞的DNA傷害程度則是由彗星試驗 (comet assay) 來評估。我們的結果顯示，抽菸、綠茶飲用、暴露於炒菜油煙、肺癌家族史和DNMT3B -149 基因型是相關於增加的肺癌危險。肺癌病例的平均DNA尾動量 (DNA tail moment) 為1.31 (± 0.75，標準差) µm，相較於健康對照的1.01 (± 0.33) µm，呈現顯著較高的DNA傷害程度 (P < 0.01)。進一步地，在調整可能干擾因子的效應後，具有DNA傷害高度程度者相較於具有DNA傷害低度程度者呈現出2.77倍的肺癌發生危險性 (95% confidence interval [C.I.] = 1.66-4.63)。以攜帶DNMT3B -149 CT基因型之非抽菸者做為參考組 (odds ratio [OR] = 1.00)，攜帶DNMT3B -149 TT基因型之抽菸者具有顯著較高的肺癌發生危險性 (OR = 2.89，95% C.I. = 1.17-7.12)；抽菸與DNMT3B -149 基因型對於肺癌發生危險具有顯著的交互作用存在。同樣地，選取DNA傷害低度程度之非抽菸者做為參考組 (OR = 1.00)，則DNA傷害中度程度之抽菸者 (OR = 6.22，95% C.I. = 2.38-16.29) 以及DNA傷害高度程度之抽菸者 (OR = 13.47，95% C.I. = 5.53-32.83) 分別具有顯著較高的肺癌發生危險；抽菸與個體的DNA傷害程度對於肺癌發生危險的顯著交互作用也被觀察到。然而，綠茶飲用、DNMT3B -149 基因型與DNA傷害程度分別對於肺癌發生危險性的交互作用並未達到統計顯著性。我們的結果建議著，啟動子活性較高的DNMT3B -149 TT基因型可能增加因抽菸所引起的肺癌發生危險；並且較嚴重的DNA傷害程度也可能會增加抽菸所導致的肺癌發生危險性。
Lung cancer is one of the major cancers in the world. Smoking can cause an increase in the stability of DNA methylation, thereby promoting tumor suppressor gene hypermethylation, and presenting sensitivity for carcinogens, thus being easily induced DNA damage. DNA methyltransferase (DNMT) 3B is a member of DNMT family. Specially, antioxidant tea polyphenols may be able to inhibit DNMT activity, thereby decrease tumor development. Therefore, we designed a case-control study to evaluate the effects of smoking, green tea consumption, and DNMT3B -149 genetic polymorphisms on DNA damage and the risk of lung cancer occurrence. In total, 190 cases with primary lung cancer and 380 healthy controls were recruited in this study. Questionnaires were administered to obtain demographic characteristics, cigarette smoking habits, green tea consumption, intake of fruits and vegetables, cooking practices, and family history of lung cancer. The genotypes for DNMT3B -149 were identified by polymerase chain reaction, and cellular DNA damage level was evaluated by comet assay. Our results revealed that smoking, green tea consumption, exposure to the fume of cooking, family history of lung cancer, as well as DNMT3B -149 genotypes were associated with elevated lung cancer risk. The mean DNA tail moment for lung cancer cases was 1.31 (±0.75, standard deviation) µm, and presenting a significantly higher level of DNA damage as compared to 1.01 (±0.33) µm of healthy controls (P < 0.01). Furthermore, after adjusting the effects of potential confounding factors, individuals with high level of DNA damage compared with those with low level of DNA damage showed a 2.77-fold risk of lung cancer (95% confidence interval [C.I.] = 1.66-4.63). When nonsmokers with the DNMT3B -149 CT genotype were selected as the reference group (odds ratio [OR] = 1.00), smokers who carrying the DNMT3B -149 TT genotype had a significantly higher risk of lung cancer occurrence (OR = 2.89, 95% C.I. = 1.17-7.12). There was a significant interaction between smoking status and DNMT3B -149 genotypes on lung cancer risk. Similarly, nonsmokers with low level of DNA damage were selected as the reference group (OR = 1.00), smokers with moderate level of DNA damage (OR = 6.22, 95% C.I. = 2.38-16.29) and smokers with high level of DNA damage (OR = 13.47, 95% C.I. = 5.53-32.83) had a significantly higher risk of lung cancer occurrence, respectively. The significant interaction between smoking status and DNA damage level on lung cancer risk was also observed. However, the interactions between green tea consumption, DNMT3B -149 genotypes, and DNA damage level on lung cancer risk did not reach a statistical significance, respectively. Our results suggested DNMT3B -149 TT genotype which had a higher promoter activity could increase lung cancer risk elicited by cigarette smoking; and heavier level of DNA damage might be also increase lung cancer risk induced by cigarette smoking. |
| URI: | https://ir.csmu.edu.tw:8080/ir/handle/310902500/5784 |
| Appears in Collections: | [公共衛生學系暨碩士班] 博碩士論文
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