人類細胞色素P450 2J2 G-50T基因多型性與血管加壓素轉化酶插入/缺失基因多型性引發口腔癌及癌前病變相關性之探討

Cytochrome P450 2J2 gene G-50T polymorphism and angiotensin-converting enzyme gene insertion/deletion polymorphism in oral cancer and precanceous patients

劉漢邦(Han-Pang Liu)

指導教授 ： 謝天渝

高雄醫學大學/口腔醫學院/牙醫學研究所/碩士(2009年)

摘要

研究目的：
許多研究指出慢性發炎浸潤及自體免疫反應都與口腔黏膜病變有關。血管加壓素轉化酶(ACE)參與許多組織的發炎反應，對於細胞的生長及重塑具有重要性，人類細胞色素P450 酶2J2 (CYP2J2)在cis-epoxyeicosatrienoic acids（EETs）的生物合成中扮演重要的角色，而EET是一個很強的發炎抑制劑。本研究欲探討血管加壓素轉化酶(ACE)插入/缺失(I/D)基因多型性及人類細胞色素P450酶2J2(CYP2J2) G-50T基因多型性與口腔癌患者、口腔癌前病變患者(實驗組)和無口腔黏膜病變者之檳榔嚼食者之關聯性。並進一步探討ACE I/D 基因多型性、CYP2J2 G-50T基因多型性與口腔癌疾病嚴重程度之相關性。
研究方法：
以高雄醫學大學附設中和紀念醫院口腔顎面外科經病理診斷確定為口腔癌患者182位及口腔癌前病變患者110位作為研究實驗組，另以男子監獄受刑人中有菸酒檳榔習慣十年以上但無口腔黏膜疾病者128位作為對照。收集其基本資料後採集靜脈全血進行DNA 萃取，利用聚合酶連鎖反應(Polymerase chain reaction)進行ACE
I/D及CYP2J2 G-50T基因多型性分析。

結果：
ACE I/D 基因多型性在口腔癌組分佈 II:ID:DD分別為44.0%:32.4%: 23.6%, 在口腔癌前病變組分別為45.6%:34.6%: 20.0%，與對照組II:ID:DD =55.5%:37.5%:7.0%比較下，在口腔癌組及口腔癌前病變組中皆有統計上的差異(p-value<0.05)。CYP2J2 G-50T基因多型性在口腔癌組分佈 GT/TT:GG 分別為13.2%:86.8%, 在口腔癌前病變組分別為5.4%:94.6%，與對照組GT/TT:GG =6.3%:93.8%比較下，在口腔癌組有統計上的差異(p-value<0.05) 但口腔癌前病變組則無(p-value=0.7948)。在口腔癌患者中，ACE DD基因型可能在頭頸部淋巴有轉移的傾向(p-value=0.0337)。
結論：
血管加壓素轉化酶的基因多型性在口腔癌患者及口腔癌前病變患者對嚼食檳榔但無病變的對照組有顯著較高比率的DD 基因型，對於口腔癌及癌前病變為危險因子。另外DD 基因型亦會與口腔癌頭頸部淋巴轉移相關(p-value=0.05)。人類細胞色素P450酶2J2 G-50T基因多型性在口腔癌患者中有較高比率的GT/TT基因型，屬於危險因子但對口腔癌前病變患者則無顯著之關聯性。

關鍵字

血管加壓素轉化酶人類細胞色素P450酶2J2 ； 基因多型性 ； 感受性 ； 口腔癌 ； 檳榔

並列摘要

Objective：
Angiotensin-converting enzyme (ACE) is expressed in a wide range of tissues. It may be involved in various steps of the inflammatory response. Cytochrome P450(CYP)2J2 metabolizes arachidonic acid to epoxyeicosatrienoic acids(EETs). The EET are potent inhibitors of inflammation. We want to investigate the connection among ACE I/D gene polymorphism, CYP2J2 G-50T gene polymorphism , oral cancer patient and oral precancer patient compared with non-oral mucosal lesion subject with betel nut chewing habit control group. We also test the hypothesis that ACE I/D gene, CYP2J2 G-50T gene polymorphism participate in oral cancer disease severity.
Materials & Methods：
Using genomic DNA from 182 patients with oral cancer(most are
squamous cell carcinoma)and 110 patients with oral precancer. we assessed the ACE I/D gene polymorphism and CYP2J2 G-50T gene polymorphism by PCR analysis and compared with control population (n =128)
Results：
ACE genotypes are distributed in oral cancer patients, precancer patients and control subjects as follow; oral cancer II:ID:DD=44.0%:32.4%: 23.6%, oral precancer II:ID:DD= 45.6%:34.6%: 20.0%, control group II:ID:DD =55.5%:37.5%:7.0% and significantly associated with a higher risk of both disease (p-value<0.05)。In oral cancer patients, trend was observed between ACE DD genotypes and lymph node metastasis in head and neck region(p-value = 0.0337). CYP2J2 G-50T genotypes are distributed in oral cancer patients, precancer patients and control subjects as follow; oral cancer GT/TT:GG =13.2%:86.8%, oral precancer GT/TT:GG =5.4%:94.6%，control group GT/TT:GG =6.3%:93.8%. CYP2J2 G-50T GT/TT genotypes are significantly associated with a higher risk of oral cancer(p-value<0.05) but not in oral precancer(p-value=0.7948)。
Conclusions：
ACE I/D gene polymorphism presents higher frequency in oral cancer
patients and precancer patients than in cancer-free subjects. And the further analysis suggests the relation between ACE DD genotype and lymph node metastasis. CYP2J2 G-50T gene polymorphism presents higher frequency in oral cancer patients than in cancer-free subjects but not in precancer patients.

並列關鍵字

Angiotensin-converting enzyme ； Cytochrome P450(CYP)2J2, ； gene polymorphism ； susceptibility ； oral cancer ； betel nut

參考文獻

參考文獻

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