2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38558According to the 2005 report of department of health (Taiwan), lung cancer has been the second and first leading cause of cancer deaths for males and females, respectively. In Taiwan, 1980-1989, the 5-year survival rates: 44% for stage I, 36% for stage II, 7% for stage III, and 0% for stage IV patients. Post-operative adjuvant therapy could not improve the prognosis of lung cancer patients. These causes of poor survival rates are due primarily to tumor recurrence and metastasis. Thus, the diagnosis and prevention for tumor recurrence and/or metastasis is very important for improving the prognosis of advanced lung cancers. Environmental chemicals might be one of etiologies for human lung cancers. Of these chemicals, tobacco smoke (benzo[a]benzene, BaP, as representative) and dioxins (TCDD as representative) increased the risk for lung cancers shown in epidemiological data. BaP and TCDD are aryl hydrocarbon receptor (AhR) ligands. Liganded AhR is metabolically activated by cytochrome P450 (CYP) enzymes in target cells to form DNA adducts, leading to cell transformation if DNA repair fails. Some animal studies provided the evidence on the carcinogenicity of BaP and TCDD in an AhR-dependent pathway. AhR and CYP1B1 overexpression in bronchioloalveolar carcinoma and adenocarcinoma compared with adjacent bronchiolar epithelia of lung. AhR signaling pathway might be involved in the development of lung cancers. Studies showed that genetic alterations of AhR affected AhR protein expression. Moreover, hypomethylation of CYP1B1 promoter region lead to CYP1B1 up-regulation in human prostatic adenocarcinomas. Therefore, genetic alterations of AhR and CYP1B1 are suggested to affect AhR and CYP1B1 protein expressions. Since the differential expression of CYP1B1 or AhR has been observed between normal mucosa and neoplasms, AhR or CYP1B1 is suitable to be marker for screening secondary lung cancers. Thus, the objective of this study is to investigate the possibility of aberrant methylation of AhR or CYP1B1 as a screening marker for detecting recurrent and metastasis of lung cancers.2005 年衛生署〈台灣〉公佈肺癌分居男女癌症死因的第二位與第一位。1980-1989，台 灣流行病學資料指出肺癌5 年存活率：第一期44%，第二期36%，第三期7%，第四期 0%；並且，術後的輔助治療無法改善疾病預後；主要的原因是腫瘤復發與轉移。因此 腫瘤復發與轉移的診斷與預防對於改善肺癌的預後是很重要的。環境化學毒物是肺癌的 致病因之一。環境化學毒物包括抽煙煙霧(BaP 是代表物) 與戴奧辛(TCDD 是代表 物)。流行病學的資料顯示，他們會增加民眾得肺癌的危險性。BaP 與TCDD 是多環芳 香烴受器(AhR) 之配基。BaP 與TCDD 活化AhR 後，經過細胞色素P450 酵素(CYP) 代謝產生DNA adducts，如果DNA 修復系統無法有效移除DNA adducts，則細胞可能發 生惡性轉化。動物實驗證實BaP 與TCDD 具有致癌性且經由AhR 訊息傳遞路徑。因此， 致癌性AhR 配基之暴露可能藉由他們的AhR 受器與特定CYP 表現參與癌化過程。最 近，我們的實驗結果發現AhR/CYP1B1 過度表現主要發生在肺支氣管肺泡上皮癌與肺 腺癌。因此，AhR 訊息傳遞路徑可能參與肺癌癌化過程，並且推測AhR 與CYP1B1 基 因的改變可能是導致AhR 與CYP1B1 蛋白質表現異常的原因。實驗證實AhR 基因的改 變會影響AhR 的表現。近來實驗更發現前列腺癌細胞的CYP1B1 promoter 有 hypomethylation 的現象，因而導致CYP1B1 的過度表現。既然AhR 與CYP1B1 在正常 上皮與腫瘤有基因上的差別性表現，因此可以應用這種現象做為診斷肺癌或預防腫瘤復 發與轉移之生物標記。本研究的目的是探討AhR 與CYP1B1 基因表現當作肺癌診斷或 預防腫瘤復發與轉移之生物標記的可能性。多環芳香烴受器肺癌細胞色素P4501B1甲基化預防Aryl hydrocarbon receptorLung cancerCytochrome P4501B1PromotermethylationPreventionProject