環境危險因子、發炎相關細胞激素基因的基因多型性與食道癌之相關性研究

Environmental Hazards, Genetic Polymorphisms of Inflammatory Cytokine Genes and Esophageal Cancer Risks

楊顓維(Chuan-Wei Yang)

指導教授 ： 吳明蒼

高雄醫學大學/健康科學院/職業安全衛生研究所/碩士(2006年)

https://doi.org/10.6832/KMU.2006.00112

摘要

過去我們的研究發現，抽菸、喝酒與嚼食檳榔都是食道癌的危險因子，而受幽門螺旋桿菌感染是食道癌的保護因子。但是還不清楚這些環境危險因子是如何影響食道癌的發生。

目的：本研究目的在探討發炎反應過程中佔有重要角色的細胞激素基因，如腫瘤壞死因子(TNFα-857)、介白素-1(IL1β-31)、介白素-1β拮抗因子(IL1 RN)的基因多型性與食道癌間的相關研究。

材料與方法：本研究設計採用醫院為主的病例對照研究法，從民國八十五年八月到九十五年四月，分別從高雄醫學大學附設中和紀念醫院與高雄榮民總醫院收集個案，共收集經由醫生診斷確定為新發生的鱗狀上皮細胞癌之食道癌患者223位為病歷組，其243位對照組來自相同醫院的健康檢查中心，並經由醫生診斷確定無癌症病史之個案，並以年齡 (±3歲) 及性別進行配對。利用聚合酶連鎖反應之方法判定腫瘤壞死因子(TNFα-857)、介白素-1(IL1β-31)、介白素-1β拮抗因子(IL1 RN)的基因型。

結果：本研究結果發現抽菸、喝酒與嚼食檳榔，會增加罹患食道癌的危險性；而感染幽門螺旋桿菌對於食道癌形成保護作用，會降低罹患食道癌的危險性。發炎相關細胞激素基因的基因多型性部份，在調整過可能的干擾因子之後，結果發現IL-1β-31帶TT基因型者相對於帶CC基因型者，罹患食道癌的危險性為1.59倍(95% CI, 0.67-3.78)；TNF-α-857帶TT基因型者相對於帶CC基因型者，罹患食道癌的危險性為1.16倍(95% CI, 0.67-3.78)；IL-1RN帶2R allele者相對於帶其他allele者，罹患食道癌的危險性為1.55倍(95% CI, 0.62-3.88)。基因與環境危險因子的交互作用部分，發現在沒有喝酒的人中，IL-1β-31帶TT基因型者相對於帶CC基因型者，罹患食道癌的危險性為4.15倍(95% CI, 0.97-17.84, p=0.055)。

結論：本研究結果顯示發炎相關細胞激素基因的基因多型性與罹患食道癌並無顯著之相關性，且發現環境危險因子與發炎相關細胞激素基因亦無交互作用關係。過去有研究發現食道癌的發生可能是因為氧化傷害(oxidative damage)所造成的，造成氧化傷害可能與胃食道逆流、抽菸或飲食有相關，但是胃食道逆流所引起的食道癌是以腺癌為主，故發炎相關細胞激素基因與罹患鱗狀上皮細胞癌之食道癌間的關係宜再進一步探討。

關鍵字

食道癌 ； 腫瘤壞死因子 ； 介白素-1 ； 基因多型性

並列摘要

Our research group has found that cigarette smoke, alcohol consumption, and betel nut chewing are the risk factors for esophageal cancer. In contrast, H. pylori infection can protect form the development of esophageal cancer.

Objective: In this study, we investigated the association between the genetic polymorphism of inflammatory cytokine genes (TNFα-857, IL-1β-31 and IL-1RN) and esophageal cancer risks in the Taiwanese population.

Method: A hospital-based case-control study was conducted. Between August, 1996 and April, 2006, 223 newly-diagnosed esophageal squamous cell carcinoma and 243 controls were recruited from Kaohsiung Medical University Hospital (KMUH) and Kaohsiung Veterans General Hospital (KVGH). Controls were matched to the cases by age (±3 years) and sex. The TNFα-857, IL-1β-31 and IL-1RN polymorphisms were genotyped using a method of PCR-RFLP.

Results: In this study, we found increasing risk of cigarette smoking, alcoholic consumption and areca chewing on esophageal cancer risk. However, individuals with positive H. pylori infection had significantly effect to decrease esophageal cancer. After adjusted for appropriate covariates, individuals with IL-1β-31TT had a 1.59-fold risk (95% CI, 0.67-3.78) to develop esophageal cancer than those with IL-1β-31CT. Individuals with TNFα-857TT had a 1.16-fold risk (95% CI, 0.67-3.78) to develop esophageal cancer than those with TNFα-857CT. Individuals with IL-1RN 2R allele had a 1.55-fold risk (95% CI, 0.62-3.88) to develop esophageal cancer than those with IL-1RN other alleles.

Conclusion: Our results suggest polymorphisms of TNFα-857, IL-1β-31 and IL-1RN can’t modify the influence of inflammation on esophageal cancer risk. There was also no association between environmental hazards and genetic polymorphism of inflammatory cytokine genes on esophageal cancer risk. Some studies found that oxidative damage may induce esophageal cancer and the association between influence of inflammation and the risk of esophageal cancer may be relation to gastro-esophageal reflux disease, diet or smoking. Although gastro-esophageal reflux disease and adenocarcinoma esophageal cancer has been certified. Those results suggest that we need more evidence to discuss the relationship between esophageal cancer and inflammatory cytokine genes.

並列關鍵字

esophageal cancer ； tumor necrosis factor ； interleukin-1 ； polymorphism

參考文獻

衛生署，2004

Barbara, J.A., Van ostade, X. and Lopez, A., 1996. Tumour necrosis factor-alpha (TNF-alpha): the good, the bad and potentially very effective. Immunol Cell Biol, 74(5): 434-43.

Chang, Y.W. et al., 2005. Interleukin-1B (IL-1B) polymorphisms and gastric mucosal levels of IL-1beta cytokine in Korean patients with gastric cancer. Int J Cancer, 114(3): 465-71.

Chitra, S., Ashok, L., Anand, L., Srinivasan, V. and Jayanthi, V., 2004. Risk factors for esophageal cancer in Coimbatore, southern India: a hospital-based case-control study. Indian J Gastroenterol, 23(1): 19-21.

Dinarello, C.A., 1996. Biologic basis for interleukin-1 in disease. Blood, 87(6): 2095-147.