物質使用及酒精代謝基因對二次上氣消化道癌症之效應

Effects of Substance Use and Alcohol Metabolizing Genes on Second Primary Cancer of Upper Aerodigestive Tract

洪韻如(Yun-Ju Hung)

指導教授 ： 李建宏

高雄醫學大學/健康科學院/公共衛生學研究所/碩士(2013年)

https://doi.org/10.6832/KMU.2013.00051

摘要

背景：
近年來醫療科技進步，但並沒有改善上氣消化道癌症病人的存活率，究其主要原因為上氣消化道癌症病人在治療後仍然發生二次原發性癌症。
研究目的：
本研究探討物質使用、酒精代謝基因對二次上氣消化道癌症發生風險、發生年齡的效應，並進一步分析二次上氣消化道癌症與死亡的關係。
材料與方法：
本研究為同期世代研究，於1992年6月到2011年3月，在高雄醫學大學附設中和紀念醫院，招募上氣消化道癌症病人參與本研究，樣本數共計399位。在一次上氣消化道癌症確診時，我們採集病人的血液檢體，查詢病人的臨床醫療紀錄，並對病人作問卷訪視調查菸酒檳榔使用特質。然後，以窄頻影像內視鏡追蹤病人有無發生二次上氣消化道癌症，以高醫病歷室電子查詢系統追蹤病人有無發生死亡。
結果：
研究結束（2013年1月）時，在399位病人當中共計59位（14.8%）發生二次上氣消化道癌症。檳榔終生暴露量≧800顆年者比起無檳榔使用習慣者對異時二次癌症的發生風險為3.8倍（95% C.I. of aHR：1.1-13.3），檳榔開始嚼食年齡<20歲者、檳榔每日攝取量≧30顆/日者、檳榔終生暴露量≧800顆年者比起無檳榔使用習慣者對二次口腔癌症的發生風險分別為5.4倍（95% C.I. of aHR：1.2-24.6）、4.4倍（95% C.I. of aHR：1.0-18.9）、5.4倍（95% C.I. of aHR：1.3-22.7）。檳榔開始嚼食年齡<20歲者比較早發生異時二次癌症、二次口腔癌症的風險分別是無檳榔使用習慣者的4.9倍（95% C.I. of aHR：1.3-19.4）、10.5倍（95% C.I. of aHR：1.0-111.9）。攜帶ADH1B G/G基因型與ALDH2 A/A+A/G基因型的飲酒者比起無酒精使用習慣者對同時二次癌症、二次咽部癌症、二次食道癌症的發生風險分別為33.1倍（95% C.I. of aHR：2.0-536.2）、41.3倍（95% C.I. of aHR：1.8-927.2）、10.7倍（95% C.I. of aHR：1.1-100.9）。有二次上氣消化道癌症者比起沒有二次上氣消化道癌症者對死亡的風險為4.5倍（95% C.I. of aHR：2.4-8.3）。
結論：
二次口腔癌症發生風險、發生年齡與檳榔使用的特質有關。攜帶ADH1B G/G基因型與ALDH2 A/A+A/G基因型的飲酒者發生二次咽部癌症、二次食道癌症的風險較高。有二次上氣消化道癌症者比沒有二次上氣消化道癌症者有較高的死亡風險。

關鍵字

二次原發性癌症 ； 上氣消化道 ； 口腔 ； 咽部 ； 食道 ； 喉部 ； 同時的 ； 異時的 ； 酒 ； 檳榔 ； 香菸 ； ADH1B ； ALDH2

並列摘要

Background:
The medical technique is in advance in recent years, but it does not improve the survival rate of the patients with upper aerodigestive tract cancer. The main reason is the occurrence of second primary cancer.
Purpose:
The aim of the present study was to explore the effect of substance use and alcohol metabolizing genes on the incidence and diagnostic age of second primary cancer of upper aerodigestive tract. Furthermore, we analyzed the association between second primary cancer of upper aerodigestive tract and death.
Material and methods:
This was a concurrent cohort study. 399 patients with upper aerodigestive tract cancer were recruited in Kaohsiung Medical University Chung-Ho Memorial Hospital from June, 1992 to April, 2011. When the patients were diagnosed as first primary cancer of upper aerodigestive tract, we collected their blood samples, consulted their clinical medical records, and interviewed them with questionnaire. And then the patients were followed up to ascertain the occurrence of second primary cancer of upper aerodigestive tract and the occurrence of death.
Results:
59 out of the 399 recruited patients suffered from second primary cancer of upper aerodigestive tract when the study ended. The incidence risk of metachronous second primary cancer in betel-quid lifetime exposure ≧800 quid-year chewers was 3.8 (95% C.I. of aHR: 1.1-13.3) times higher than in non-chewers. The incidence risk of second primary cancer of oral cavity in betel-quid starting age <20 years chewers, in betel-quid daily quantity ≧30 quid/day chewers, and in betel-quid lifetime exposure ≧800 quid-year chewers were respectively 5.4 (95% C.I. of aHR: 1.2-24.6), 4.4 (95% C.I. of aHR: 1.0-18.9), and 5.4 (95% C.I. of aHR: 1.3-22.7) times higher than in non-chewers. In addition, the early-onset risk of metachronous second primary cancer and second primary cancer of oral cavity were respectively 4.9 (95% C.I. of aHR: 1.3-19.4) and 10.5 times (95% C.I. of aHR: 1.0-111.9) higher in betel-quid starting age <20 years chewers than in non-chewers. The incidence risk of synchronous second primary cancer, second primary cancer of pharynx, and second primary cancer of esophagus were respectively 33.1 (95% C.I. of aHR: 2.0-536.2), 41.3 (95% C.I. of aHR: 1.8-927.2), 10.7 (95% C.I. of aHR: 1.1-100.9) times higher in alcohol drinkers with ADH1B G/G genotype and ALDH2 A/A+A/G genotype than in non-drinkers. Patients with second primary cancer of upper aerodigestive tract experienced a 4.5-fold (95% C.I. of aHR: 2.4-8.3) higher death risk than those who did not suffer from second primary cancer of upper aerodigestive tract.
Conclusions:
We found that betel-quid consumption characteristics were associated with the incidence and diagnostic age of second primary cancer of oral cavity, and that alcohol drinkers with ADH1B G/G genotype and ALDH2 A/A+A/G genotype had the higher incidence risk of second primary cancer of pharynx and esophagus. Moreover, people who were attacked by second primary cancer of upper aerodigestive tract had higher death risk than those without second primary cancer of upper aerodigestive tract.

並列關鍵字

second primary cancer ； upper aerodigestive tract ； oral cavity ； pharynx ； esophagus ； larynx ； synchronous ； metachronous ； alcohol ； betel-quid ； cigarette ； ADH1B ； ALDH2

參考文獻

1. Cooper JS, Pajak TF, Rubin P, et al. Second malignancies in patients who have head and neck cancer: incidence, effect on survival and implications based on the RTOG experience. International journal of radiation oncology, biology, physics. Sep 1989;17(3):449-456.

2. Sturgis EM, Miller RH. Second primary malignancies in the head and neck cancer patient. The Annals of otology, rhinology, and laryngology. Dec 1995;104(12):946-954.

3. Leon X, Quer M, Diez S, Orus C, Lopez-Pousa A, Burgues J. Second neoplasm in patients with head and neck cancer. Head & neck. May 1999;21(3):204-210.

4. Do KA, Johnson MM, Doherty DA, et al. Second primary tumors in patients with upper aerodigestive tract cancers: joint effects of smoking and alcohol (United States). Cancer causes & control : CCC. Mar 2003;14(2):131-138.

5. Alvarez Marcos CA, Llorente Pendas JL, Franco Gutierrez V, et al. Second primary tumors in head and neck cancer. Acta otorrinolaringologica espanola. Dec 2006;57(10):462-466.