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系統識別號 U0026-1502201700360100
論文名稱(中文) 血中維生素D濃度和腫瘤組織維生素D接受器的表現情形在大腸直腸癌致癌機轉所扮演的角色
論文名稱(英文) Role of serum vitamin D level and tumor vitamin D receptor expression in colorectal carcinogenesis
校院名稱 成功大學
系所名稱(中) 臨床醫學研究所
系所名稱(英) Institute of Clinical Medicine
學年度 105
學期 1
出版年 106
研究生(中文) 康瑞文
研究生(英文) Jui-Wen Kang
學號 S97011072
學位類別 碩士
語文別 中文
論文頁數 58頁
口試委員 指導教授-林錫璋
口試委員-許博翔
口試委員-蘇五洲
口試委員-陳炯瑜
中文關鍵字 大腸癌  大腸進階型腺瘤  維生素D  維生素D接受器  大腸癌危險因子  大腸癌預後因子 
英文關鍵字 Colorectal cancer  vitamin D  vitamin D receptor  risk factors of colorectal cancer  prognostic factors of colorectal cancer 
學科別分類
中文摘要 大腸癌在世界及台灣都是一個很重要的疾病,僅管對發生大腸癌的危險因子及其致病機轉已經越來越清楚,世界各地推廣大腸癌篩檢也不遺餘力,然而目前的流行病學統計除了美國以外,世界各地大腸癌的發生率仍然呈現上升的趨勢;即便在美國,年輕族群大腸癌的發生率也仍在上升。因此如何在找到更多更有證據的預防因子或篩檢的工具變成為防治大腸癌的重點。維生素D與大腸癌的關係最主要來自於有研究指出大腸癌的發生率與緯度及紫外線輻射量有關係,而體內維生素D最主要是皮膚經由日曬而產生,經過肝臟、腎臟及大腸組織而活化;後續研究也證實血中維生素D濃度低有較高產生大腸癌的風險,大腸癌患者若血中維生素D濃度較低的話預後也較差;而維生素D需要維生素D接受器才能發揮作用,也有研究指出維生素D接受器表現的情形也跟產生大腸癌的風險及預後有關。目前少有研究同時探討維生素D與維生素D接受器在大腸癌進展或轉移的關係。因此本研究想探討維生素D與維生素D接受器在大腸直腸腫瘤不同期別的變化,並評估其在大腸癌的危險因子及預後因子所扮演的角色。本研究的第一部分發現相較大腸腺瘤的病人而言,大腸癌的病患較容易有血中維生素D不足的情形;若以期別來看的話,血中維生素D的濃度在第四期大腸癌的病人才明顯偏低;在大腸癌危險因子的多變量分析中,血中維生素D濃度不足(< 30 ng/mL)會增加大腸癌的風險(OR: 3.13, 95% CI:1.25-7.81, p=0.015)。而維生素D接受器的表現在癌前病變的表現強烈,而一但進展到腺癌表現便減弱;維生素D接受器表現量的高低。至於大腸直腸癌的預後因子評估,我們短期的追蹤研究無法證實維生素D缺乏(< 20 ng/mL)或維生素D接受器表現微弱(< 10%)可以做為評估預後的預測因子。而維生素D接受器表現微弱(< 10%)也無法預測淋巴結轉移的風險,只有淋巴管或血管侵犯(lymphovascular invasion) 及有神經旁側侵犯(perineural invasion)可以預測淋巴結轉移。
總結來說,血中維生素D濃度不足(< 30 ng/mL)可能會增加大腸癌的風險,然而血中維生素D濃度與維生素D接受器表現均在大腸直腸腫瘤癌化的過程所扮演的角色仍需根據不同的期別去做更長期的追蹤才會更清楚其臨床應用的價值。
英文摘要 Colorectal cancer is one of the most common cancer and leading causes of cancer death worldwide. Although colorectal cancer can be prevented by risk factors modifications and colon cancer screening, its incidence still increase worldwide. The epidemiologic and observational studies have suggested the potential role of vitamin D in colon cancer prevention. Populations with lower serum vitamin D level have increased risks of colorectal cancer. Colorectal cancer patients with lower serum vitamin D level have worse prognosis.
Anticancer effects of vitamin D are mediated by the vitamin D receptor (VDR). Therefore, VDR expression is an important factor of cell responsiveness of vitamin D. Some studies report that lower VDR expression in colorectal cancer is associated with poor prognosis.
The aim of present study was to investigate the association of serum vitamin D level and tumor VDR expression in different stages of colorectal cancer. We found that serum vitamin D level decreased significantly in stage IV patients. However, tumor VDR expression decreased significantly in patients with earlier stage of colorectal cancer. Vitamin D insufficiency (< 30 ng/mL) seemed an independent risk factor of colorectal cancer. In survival analysis, neither lower serum vitamin D level nor lower tumor VDR expression were prognostic factors of colorectal cancer. Lower tumor VDR expression could not predict lymph node metastasis. Further long-term follow up was needed to clarify the role of serum vitamin D level and tumor VDR expression in each stage of colorectal cancer.
論文目次 目 錄
中文摘要 I
英文摘要 (Extended bstract) III
誌謝 VII
目 錄 VIII
圖目錄 IX
表目錄 X
符號與縮寫對照表 XI
儀器、藥品及試劑名稱 XII
第一章  緒論 1
第二章 材料與方法 13
第一節  研究架構 13
第二節  資料收集 14
第三節  統計方法 21
第三章  研究結果與討論 23
第一節  研究結果 23
第二節  討論 30
第三節  總結 33
參考文獻 34
附 錄 41

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