台湾地区口咽恶性肿瘤及槟榔块分析之流行病学研究

【外文题名】The epidemiology study of oropharyngeal carcinoma and areca quid in Taiwan

【作者】 陈丙何

【关键词】 L phenylalanine meta tyrosine ortho tyrosine HPLC LC MS 荖花槟榔 荖叶槟榔 槟榔子 荖花 红灰 荖叶 白灰 氢氧基 种族 嚼食槟榔 淋巴恶性肿瘤 涉险比值 性别 死亡率 存活率 口咽恶性肿瘤

【外文关键词】 LC MS HPLC ortho tyrosine meta tyrosine L phenylalanine betel quid chewing survival mortality survival lymphoma oropharyngeal carcinoma hazard ratio gender

【导师姓名】蔡吉政

【学位名称】博士

【学位年度】暂无

【学位授予单位】暂无

【所属分类】O121.2,Q954.56,R18,R195.3,Q10

【录入时间】2014-11-17

【全文挂接】 读秀挂接

【摘要】及死於全部死因兩大類。研究個案的五年存活率 (Five-year survival rates)是由Kaplan-Meier methods來加以估算，另外用Cox proportional-hazards model來確定性別因素在各個臨床變項的影響。經由口咽惡性腫瘤死因及全部死因的五年存活率分析，我們發現男性的存活率顯著性的低於女性。在口咽惡性腫瘤死因方面，調整過的涉險比值(hazard ratio)，男性相對於女性為1.54倍(95% CI: 1.36-1.74)。而在全死因方面，男性為女性的1.44 倍(95% CI: 1.31-1.58)。以發生部位來看，研究個案中罹患舌惡性腫瘤者的預後最差。在腫瘤型態方面，淋巴惡性腫瘤(lymphoma)的死亡危險性最低。在年齡分層方面，老年人的存活率最差。在治療方式方面，僅單獨接受手術治療者的存活率最高。經由上述的研究結果，我們認為性別與其他相關的臨床因子在口咽惡性腫瘤的存活率方面具有重要的角色。我們建議臺灣地區如此顯著性的性別存活率差異，可能跟男性的高檳榔嚼食率有關。
口咽惡性腫瘤具有種族的差異性，臺灣地區是一個檳榔嚼食盛行率高的地區，並且在大多數的惡性腫瘤方面我們可以發現有種族上的差異性存在。我們的研究目的在於確認種族的差異性以及在每一種族中預後因子所扮演的角色，與口咽惡性腫瘤存活的相關性。我們總共收集了自1985年到1994年間的口咽惡性腫瘤發生個案共9749人。研究個案中死因為口咽惡性腫瘤者才歸入我們的研究分析中。不同種族間五年存活率的估算是經由Kaplan-Meier 的方法以及存活曲線差異的顯著性是由log-rank test來加以檢定。Cox proportional-hazards model來檢驗預後因在每一族別存活上所扮演的角色。閩南族群(Hokkien)及臺灣原住民(Taiwanese aborigines)罹患口咽惡性腫瘤的五年存活率分別為59.9%及62.8%，顯著性的低於客家人(65.3%)。在經由所有預後因子的調整下，臺灣原住民死於口咽惡性腫瘤的危險性為客家人的1.10倍(95%CI, 0.89-1.36)；而閩南人死於口咽惡性腫瘤的危險性為客家人的1.17倍(95%CI, 1.02-1.34)。研究個案罹患舌部或口部惡性腫瘤者的預後較差；相反的罹患淋巴瘤者的預後則最佳。再年紀越大的年齡層其預後越差，研究個案若是接受手術治療者其預後最佳。經由上述的研究結果我們可以發現，種族及其他相關的預後因子(例如:診斷年代、性別、診斷年齡、解剖學發生部位、腫瘤型態以及治療方式)可能在口咽惡性腫瘤的存活表現上扮演了一個重要的角色以及其死亡的危險性有可能會增高，例如在偏好使用檳榔的閩南人及客家人。
臺灣地區嚼食檳榔是相當普遍的習慣，過去的許多流行病學研究指出嚼食檳榔(areca quid (AQ))和口腔病變的發生有密切、直接的關係。臺灣檳榔塊大致上可分為荖花檳榔塊(Lao-hwa quid)及荖葉檳榔塊(Betel quid)兩種。荖花檳榔塊主要是由檳榔子(areca nut (AN))、荖花(inflorescence of Piper Betle Linn. (IPB))以及紅灰(red lime)所組成。而荖葉檳榔塊是由檳榔子、荖葉(Piper betle leaf (PBL))以及白灰(white lime)所組成。有幾篇研究報告指出，檳榔萃取物質可以在鹼性的條件下產生活性氧屬物質(reactive oxygen species (ROS))，例如: 氫氧基(hydroxyl radical (HO˙))，且過渡金屬離子會催化此氧化作用。檳榔成分物質(含石灰)所產生的氫氧基，會引起細胞的氧化作用和染色體的損害，可能會造成口腔黏膜細胞不同時期的病變過程。而且，檳榔萃取物質在鹼性的環境下會與DNA作用產生8-hydroxy-deoxyguanosine（8-OH-dG），造成DNA變性，因此可以被視為突變或病變過程的基因標記。為了研究檳榔塊是否會形成氫氧基物質，我們收集了高雄地區不同商店所購買的檳榔塊，來測定檳榔塊混和L-phenylalanine (Phe)會形成 mata-tyrosine (m-Tyr)及ortho-tyrosine (o-Tyr)，作為產生氫氧基的化學標記。最後使用HPLC來偵測其形成量，並利用LC-MS來確認其形成產物。研究結果發現荖花檳榔較荖葉檳榔產生較多的氫氧基，另外在金屬離子的作用方面，Cu2+及Fe2+會促進氫氧基的形成。我們的研究結果建議，臺灣地區不同成份的檳榔塊會對氫氧基的形成量造成不同程度的影響，尤其荖花檳榔塊所產生的氫氧基遠高於荖葉檳榔塊，因此我們推論荖花檳榔塊所含的荖花成分可能間接對口腔黏膜產生較嚴重的傷害。...

【外文摘要】Oropharyngeal carcinoma is one of the most common carcinomas in the world. In Taiwan, a clear gender difference emerges for rates of oropharyngeal carcinoma incidence. The purpose of this study was to identify the gender differences and clinical factors associated with oropharyngeal carcinoma survival rates in Taiwan. We analyzed the survival rates of 8,114 subjects diagnosed with oropharyngeal carcinoma between 1987 and 1994. Oropharyngeal carcinoma death and all-cause death outcomes were included in our study. Five-year survival rates were estimated by Kaplan-Meier methods. The Cox proportional-hazards model identified the key factors for gender according to clinical characteristics. Oropharyngeal carcinoma and all-cause specific five-year survival rates were significantly lower for males than females. The adjusted hazard ratio of males versus females was 1.54 (95% CI: 1.36-1.74) for oropharyngeal carcinoma death and 1.44 (95% CI: 1.31-1.58) for all-cause death. Subjects with tongue carcinoma presented the worst prognosis whereas lymphoma had the lowest risk of death. Prognosis was the worst among elderly subjects. Subjects treated by surgery alone had the highest survival rate. Gender and other clinical factors play important roles in oropharyngeal carcinoma survival. We suggested that Taiwanese males have high proportion of betel quid chewing to be associated with gender differences.
Oropharyngeal carcinoma, occurring in a wide variety of ethnicities, is among the most common carcinomas in the world. In Taiwan, where betel-quid chewing is popular, a distinct ethnic variation in mortality rates has been suggested for most carcinomas. The purpose of this study is to identify the ethnic differences, and the role of prognostic factors within each ethnicity, associated with the survival of oropharyngeal carcinoma in Taiwan. The survival of 9749 diagnosed subjects with oropharyngeal carcinoma in 1985-1994 was analyzed. Subjects diagnosed with death as outcome from oropharyngeal carcinoma were included. Five-year survival rates of different ethnicities were estimated by Kaplan-Meier methods, and survival curves were found to differ significantly by log-rank test. The Cox proportional-hazards model was used to examine the role of prognostic factors on ethnic survival. The five-year survival rates of oropharyngeal carcinoma were significantly poorer for Hokkien (59.9%) and Taiwanese aborigines (62.8%) compared with Hakka (65.3%). The adjusted hazard ratio of Taiwanese aborigines versus Hakka was 1.10 (95%CI, 0.89-1.36) for oropharyngeal carcinoma mortality, and 1.17 (95%CI, 1.02-1.34) for Hokkien versus Hakka. Subjects with tongue and/or mouth carcinoma presented the worst prognosis, whereas lymphoma had the best prognosis. Prognosis was also the worst in elderly subjects. Overall, subjects who underwent surgery had the highest survival rate. Ethnicity and other prognostic factors (i.e., diagnostic period, gender, diagnostic age, anatomic site, morphologic type and therapy) may play important roles in the survival of oropharyngeal carcinoma, and risk could be heightened in instance such as predilection for betel-quid usage in Hokkien and Taiwanese aborigines.
Epidemiological studies have demonstrated an association between chewing areca quid (AQ) and an increased risk of oral cancer or precancerous oral diseases in Taiwan. The major types in Taiwan are “Lao-hwa quid” and “betel quid”. The “Lao-hwa quid” was made by tender areca nut (AN), inflorescence of Piper Betle Linn. (IPB), and red lime paste. The “betel quid” is a combination of the tender AN, Piper Betle leaf (PBL) and white lime paste. Several reports documented that reactive oxygen species (ROS), such as hydroxyl radical (HO˙) was generated from AN extract and could induce oxidative DNA damage. In this study, we investigated HO˙ formation in the AQ of Taiwan. The ingredients of AQ were obtained from two typical AQ venders in Kaohsiung City (Taiwan). By adding th...