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研究生:洪信嘉
論文名稱:口腔及咽癌之流行病學研究
指導教授:陳建仁陳建仁引用關係
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:公共衛生學系
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:1997
畢業學年度:85
語文別:中文
論文頁數:160
中文關鍵詞:咽癌流行病學
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(I)台灣地區口腔及咽癌之流行病學特徵
環境暴露與個體感受性基因的獨立與交互作用是目前所重視的癌症研究課題,與環境暴露物質代謝有關的酵素主要分為第一級(phase 1)及第二級酵素(phase Ⅱ enzyme)。本研究的目的在於探討第一級酵素中的CYP2E1及第二級酵素中的GSTM1及GSTT1基因多形性對口腔癌的影響。本研究研究對象為41名口腔癌病例及123名氏族及年齡頻率匹配對照。利用其週邊淋巴球之DNA,以聚合酵素鍊鎖反應及限制片斷多形性的方法,測定CYP2E1-Rsa Ⅰ基因型及GSTM1、GSTT1基因型,並以問卷詢得環境暴露因子資料,再以對數複迴歸分析,分析基因多形性與口腔癌發生的相關性。結果顯示抽菸、飲酒及嚼檳榔等環境因子與口腔癌危險性有劑量效應關係。在單變項分析中,GSTM1及GSTT1無效基因型並皆與口腔癌無關;在多變數分析中,以GSTM1及GSTT1都為非無效型者為參考值,有其一或兩者為無效基因型者,發生口腔癌之危險比為6.7(95%信賴區間為1.24─36.16);帶有CYP2E1 c2對偶基因者,有偏高但未達顯著意義的危險性(危險比為1.89,95%信賴區間為0.72─4.94)進一步分析基因型與環境因子的交互作用,在無飲酒或嚼檳榔習慣者當中,帶有CYP2E1 c2對偶基因者,口腔癌的危險性會顯著增加(危險比分別為714.23及4.65);但在有飲酒或嚼檳榔習慣者當中,其危險比分別只有1.27及0.74。抽菸及嚼檳榔的危險比,帶有任何CYP2E1基因型者都很相近;飲酒的危險比則是帶有CYP2E1 c1/c2或c2/c2基因型者,高於帶有c1/c1基因型者。GSTM1及GSTT1基因型與抽菸、飲酒及嚼檳榔等習慣則未顯示明顯的交互作用。本研究結果顯示遺傳易感受基因多型性與口腔及咽癌的發生有關,且不同的環境暴露對其相關性有不同的影響。

(II)口腔及咽癌多重危險因子之世代追蹤研究
本研究為分析台灣地區口腔及咽癌多重危險因子的世代研究,其研究對像包含在宜蘭縣員山鄉,台北市南港區,桃園縣大園鄉,新竹縣新埔鎮、關西鎮、橫山鄉、苗栗縣竹南鎮,雲林縣斗南鎮,高雄市楠梓區,高雄縣大樹鄉,及屏東縣竹田、車城鄉12個鄉鎮的13192名大於30歲的男性。在追蹤十年共有29名口腔及咽癌新病例發生,利用Cox''s比例危害模式估計各因子的相對危險性及95%的信賴區間。結果顯示抽菸和飲酒在調整其它因子後,與口腔及咽癌的發生率呈現劑量效應的相關;咀嚼檳榔、食用豆類發酵食品頻率高(每週次數≧5次)及食用黃綠色蔬菜頻率低(每週次數≦9次)都會增加發生口腔及咽癌的危險性;食用鹽醃類食品則與口腔及咽癌無顯著相關。以無抽菸、飲酒及嚼檳榔習慣者為對照組,三種習慣都有者,發生口腔及咽癌的相對危險性高達9.59;有飲酒習慣且豆類發酵食品食用頻率≧5次者,與無飲酒習慣且豆類發酵食品食用頻率<5次者比較,發生口腔及咽癌的相對危險性為6.68。

(III)CYP2E1, GSTM1, FSTT1基因型多形性與口腔癌相關性之研究
  本研究利用台灣地區1979年至1993年口腔及咽癌發生率及1971年至1993年口腔及咽癌死亡率,探討台灣地區近二十年來口腔及咽癌長期變動趨勢、年齡及性別分布、國際及移民比較等描述流行病學特徵。分析結果顯示近二十年來,台灣地區男性口腔即咽癌發生率上升約2.7倍,而出生在1926-1934以後的世代有明顯上升的發生率,但女性發生率並未觀察到明顯的長期變化趨勢。發生率男女比由1979-1980年間的3:1上升到1991-1993年間的6:1。在35-64歲年齡層更是由3.5:1上升到7:1。死亡率之男女比更由3:1上升為13:1。1991到1993年間的發生率分析,口腔癌發生率有隨年齡上升再增加的現象,男性在55-59及75-79年齡層分別出現了兩個高峰,而女性則在75-59達到高峰。相較於印度及西方國家,台灣地區之發生率不高,但相較於各地區華人,台灣地區男性有遠高於其它地區的發生率。台灣地區男性口腔及咽癌的高發生率可能與菸草、酒類及檳榔的消費量增加有關,特別在檳榔消費上,出現與發生率相似的世代效應。本研究顯示台灣地區口腔及咽癌發生率持續上升的趨勢,並警示有效防治政策的急迫性。
(I)Epidemiological characteristics of oral and pharyngeal cancers in Taiwan
Both genetic and environmental factors are involved in the development of cancer. Some phase 1 and phase Ⅱ enzymes involved in the metabolism of carcinogens are polymorphic in genotypes. This casecontrol study focused on the associations of CYP2E1, GSTT1 and GSTM1 genotypes with oral cancer. A total of 41 oral cancer cases were recruited from National Taiwan University Hospital and 123 healthy controls frequency-matched on ethnicity and age were recruited from the community of Taipei city and county. Tobacco smoking, alcohol drinking and betel nut chewing were significantly associated with the risk of oral cancer in a does-response relationship. GSTM1 null and GTT1 null genotypes were not associated with the risk of oral cancer in the univariate analysis. In comparison with subjects whose both genotypes were non-null as the referent, those who had null genotypes of GSTT1 and/or GSTT1 had an increased risk of oral cancer (odds ratio, OR=6.7, 95% confidence interval=1.24-36.16)in the multivariate analysis. The odds ratio of developing oral cancer for those who had CYP2E1 genotype of c1/c2 or c2/c2 was 1.89 (95% confidence interval=0.72-4.94) compared with those with CYP2E1 c1/c1 genotype. Among those who had no habits of cigarette smoking and betel quid chewing, the CYP2E1 c1.c1 and c2/c2 genotypes w re associated with an increased risk of oral cancer showing Ors of 714.23 (0.05<p<0.10) and 4.65(p<0.05), repectively. The odds ratios of developing oral cancer for cigarette smoking and betel quid chewing were similar regardless CYP2E1 genotypes. Alcohol drinking was associated with a higher risk of oral cancer among subjects who had CYP2EI c1/c2 and c2/c2 genotypes than those with c1/c1 genotype.
These results suggested genetic polymorphisms of CYP2E1, GSTM1 and GSTT1 are associated with the risk of oral cancer. Different environmental factors may modify these associations.

(II) A conort study on multiple risk factors of oral and pharyngeal cancer
A cohort of 13192 male residents aged over 30 years recruited from 12 townships and precincts were studied to elucidate combinatory effects of multiple risk factors on the development of oral cancers in Taiwan. There were 29 newly-diagnosed oral cancer cases occurring in 10-year follow-up period. Cox''s proportional hazards regression model was used in estimating the relative risk and 95% confidence interval for various risk factors. The quantity of cigarette smoking and alcohol drinking were all significantly associated with oral cancer in a doseresponse relationship after adjustment for other risk factors. High consumption of fermented soy beans was another risk factor of oral cancer and the association remained significant at a borderline level (p<0.10) after multivariate adjustment. Betel quid chewing and low consumption of vegetable were associated with an increased risk of oral cancer; but the associations were not statistically significant after multivariate adjustment. No association between oral cancer risk and salted food consumption frequency was observed. Subjects who had habits of cigarette smoking, alcohol drinking and betel quid chewing had a multivariate-adjusted relative risk of 9.59 in developing oral cancer compared with those who had none of these habits. Those who had habits of alcohol drinking and consuming fermented soy beans five or more meals a week had a multivariate-adjusted relative risk of 6.68 compared with who did not drink alcohol habitually and consumed fermented soy beans less than five meals a week.

(III) Associations of genetic polymorphisms of GYP2E1, GSTM1 and GSTT1 with oral cancer
Mortality rates from 1971 to 1993 and incidence rate forni 1979 to 1993 of oral and pharyngeal cancers in Taiwan were analyzed to examine their epidemiological characteristics. In recent two decades, there was significant three-fold increase in age-adjusted incidence and mortality rates of males in Taiwan. The male-to-female ratio of incidence rate increased from 3:1 in 1979-1980 to 6:1 in 1991-1993 for all ages combined and from 3.5:1 to 7:1 for the age group of 35-64 years old. The sex ratio of mortality rate increased more strikingly from 3:1 to 13:1 during the same period. An increased incidence was among male cohorts who were born after 1926 but no obvious cohort effect was observed among females. Both motality and incidence rates of males increased with age showing two peaks at ages of 55-59 and 75-59, respectively. The incidence rate of males in Taiwan was lower than those of India and western countries, but it was higher than these of male Chinese in Hongkong, Singapore, North America, Tianjin and Shanghan. The increasing trend of oral and pharymgeal cancer among males in Taiwan paralleled th increase in the consumption of tabacco, alcohol and betel nut in past 40 years. A cohort effect of consuming beael nut similar to those of cancer incidence and mortality was also observed. These results suggested the increment in incidence and mortally rates of oral and pharyngeal cancers among males attributed to tabacco smkoing, alcohol drinking, and especially betel quid chewing. The implementation of prevention program to reduce risk of oral and pharyngeal cancers is in urgent need in Taiwan.
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