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| 題名: | 血管新生相關基因之基因多形性與泌尿道上皮癌的相關研究 |
| 作者: | 劉奇東 |
| 貢獻者: | 公共衛生學研究所 |
| 日期: | 2010 |
| 上傳時間: | 2010-10-20 11:35:17 (UTC+8) |
| 摘要: | 前言：泌尿道上皮癌(Urothelial Carcinoma，UC)包括膀胱、腎盂及輸尿管等部位的癌症，其中又以膀胱部位居多。癌症的臨床病理特性是疾病治療、預後、復發及死亡的重要指標，而血管生成的程度是影響臨床病理特性的重要因子。因此本研究目的是討論調控血管新生的四個相關基因：FIH-1、VHL、HIF-1、VEGF上五個SNP對罹病風險、臨床病理特性、復發及死亡的相關，並探討調整傳統危險因子後基因多形性對疾病的影響，以及基因多形性與傳統危險因子間交互作用與疾病的相關。
研究方法：本研究採病例-對照研究法，選取850位泌尿道上皮癌個案以及年齡、性別配對的850位健康對照，研究資料包含問卷資料、臨床病理資料。基因型判定的使用方法是PCR-RFLP及Real-time PCR。
結果：本研究結果發現抽菸、飲酒、職業暴露、砷暴露及高鹽飲食分別有2.0、1.6、1.8、1.9、1.5倍的罹病風險；職業暴露、砷暴露有2.2及1.6倍的風險發展為第二期以上癌症，若有砷暴露則增加1.7倍的死亡風險。在基因多形性與罹病的研究中發現，在抽菸者中，若VHL帶CC基因型有2.4倍的罹病風險；基因多形性與臨床病理特性的研究發現FIH帶CG或GG基因型有1.3倍風險發展為第二期以上癌症，抽菸者若VEGF-460帶有TT基因型則有1.6倍的風險發展為第二期以上癌症。
合併五個SNP的影響後發現帶有危險基因數兩個以上者其罹病風險為1.3倍，癌細胞發展為第二期以上癌症的風險是1.6倍，若有抽菸則危險基因型的影響更大，但是對細胞分化程度的影響未達顯著。
結論：血管新生相關基因之基因多形性與癌症的罹病風險、癌細胞侵犯程度、癌症的期別有關，但與細胞分化情況無統計相關。抽菸則會干擾基因多形性與泌尿道上皮癌的相關。
Introduction：
Urothelial carcinoma (UC) including bladder, renal pelvis and ureter cancer. Cancer staging and grading is the most important index for cancer prognosis, and angiogenesis is a necessary step in tumor growth and metastasis. This study was to discuss the relationship between five SNPs on the four angiogenesis-related genes：FIH-1, VHL, HIF-1, VEGF and the risk of UC morbidity, clinical pathological characteristics, recurrence, and survival rate.
Methods：
In this case - control study, we selected 850 cases of urothelial carcinoma and the age and sex matched 850 healthy controls. Data collation includes questionnaire and clinical pathological characteristics. Genotyping is determined by PCR-RFLP and Real-time PCR.
Results：
We found that Study subjects with cigarette smoking, alcohol consumption, occupational exposure, arsenic exposure, and high-salt diet have a significantly higher UC risk of 2.0, 1.6, 1.8, 1.9, and 1.5. Occupational exposure who has 2.2 times the risk of more serious clinical and pathological characteristics, arsenic exposure has 1.7 times increased risk of death.
Smokers with VHL CC genotype have a higher UC risk of 2.4. FIH with CG/GG genotype had 1.3 times risk of developing to T2 and stage II or more serious. Smokers with VEGF-460 TT genotype had 1.6 times risk of developing to stage II or more serious. Combine the five SNPs risk genes found that the number of risk genes≧2 have a higher UC risk of 1.3 and 1.6 times risk of developing to T2 and stage II or more serious. The effect of SNPs around the smokers is more obvious.
Conclusions：
These results suggested a significant association between angiogenesis-related genes polymorphisms and UC morbidity and tumor stage, but not support a significant association between SNPs and tumor grade. The cigarette smoking confounds the association between polymorphisms and UC. |
| 關聯: | 87頁 |
| 描述: | 目錄
致謝 i
表目錄 iv
圖目錄 v
中文摘要 vi
Abstract viii
第一章 緒論 1
第一節 泌尿道上皮癌的流行病學 1
第二節 臨床病理特性 2
第三節 傳統危險因子 4
第二章 文獻探討 7
第一節 癌症的生長與轉移 7
第二節 缺氧(Hypoxia)與血管新生(Angiogenesis) 8
第三節 血管新生的相關基因 9
第四節 血管新生相關基因多形性研究 14
第五節 抽菸與癌症的預後 18
第三章 研究材料與方法 19
第一節 研究目的、假設與架構 19
第二節 研究設計與資料收集 22
第三節 資料處理與分析 29
第四章 結果 31
第一節 基本人口學變項 31
第二節 傳統危險因子與泌尿道上皮癌的相關 33
第三節 基因多形性與泌尿道上皮癌的相關 49
第五章 討論 69
第六章 結論與展望 81
參考文獻 82
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