臺灣博碩士論文加值系統

細胞黏著蛋白（CDH-1）是一種細胞與細胞間黏著的分子，它能維持細胞的完整性和傳達細胞內與細胞外的訊息，所以CDH-1被認為可能與癌症的生成或是轉移有關。另一方面，細胞激素-介白素(IL)被指出與前列腺癌的免疫抑制或生成有關。我們的目的是要研究CDH-1、 IL-2和IL-2Rβ基因的多型性與前列腺癌之間的關係。我們將96位前列腺癌的病人和114位在住在相同區域的正常受試者做CDH-1、IL-2和IL-2Rβ基因多型性的比較，且追蹤病人的狀況長達五年。CDH-1和IL-2基因在前列腺癌的病人與正常受試者做比較，在基因型的分佈上有明顯的差異（各別為p<0.001和p=0.017），但在IL-2Rβ基因型的分佈上並沒有明顯的差異（p=0.388）。根據病人的年齡、病理分級、臨床分級和荷爾蒙治療的反應與基因型的分佈比較，並沒有明顯的差異。另外，IL-2基因多型性與前列腺癌的病人追蹤五年的存活分析之間的比較也無明顯的差異（log rank test, p=0.19）。因此我們認為CDH-1和IL-2基因可能是造成台灣族群形成前列腺癌的基因。

E-cadherin (CDH-1) is a cell-cell adhesive molecule which maintains cell integrity and communication between the intracellular and extracellular environment. CDH-1 may consequently be related to carcinogenesis or metastasis. And cytokines are reported to be associated with the inhibition of cancer or formation of prostate cancer. Our aim was to investigate 3’-UTR of the CDH-1 gene, C/T polymorphisms of the interleukin-2 (IL-2) gene and interleukin-2 receptor β (IL-2Rβ) gene are associated with prostate cancer. We compared the frequency of the polymorphisms of CDH-1 gene, IL-2 gene and IL-2 Rβ gene between 96 patients with prostate cancer and 114 healthy male volunteers from the same area (age >60 years). They were followed for at least 5 years. There was a significant difference in distribution of the genotype of the CDH-1 (p<0.001) and IL-2 (p=0.017) gene polymorphism between the prostate cancer group and the control group. There was no significant difference in the distribution of the genotype of the IL-2Rβ gene polymorphism between controls and cancer patients (p=0.388). There was also no significant difference according to age, pathological grading, clinical staging, and responsiveness to hormone therapy among patients. However, no significant statistical difference was found between the polymorphism of the IL-2 gene and prostate cancer in survival analysis during a 5-year follow up period (log rank test p=0.19). This study suggests that the CDH-1 and IL-2 gene may be associated with susceptibility to prostate cancer in the Taiwan population.

中文摘要 I
英文摘要 II
誌謝辭 IV
目錄 V
第一章 前言 1
第一節 前列腺的構造與功能 2
第二節 前列腺癌 3
第三節 前列腺癌的治療 7
第四節 前列腺癌預防及治療的展望 9
第五節 單核苷酸多型性 (SINGLE NUCLEOTIDE POLYMORPHISM) 11
第六節 細胞黏著蛋白與前列腺癌的關係 12
第七節 細胞激素與前列腺癌的關係 13
第八節 研究目的 14
第二章 材料與方法 16
第一節 病人的篩選 17
第二節 PCR-RFLP分析 18
第三節 KAPALAN-MEIER SURVIVAL ANALYSIS 19
第四節 統計方法 20
第三章 結果 21
第一節 CDH-1基因多型性分析的結果 22
第二節 IL-2基因多型性分析的結果 23
第四章 討論 25
第一節 CDH-1基因多型性分析的討論 26
第二節 IL-2基因多型性分析的討論 28
第三節 研究限制以及未來的展望 30
參考文獻 32
表與圖 39

Table 1. CDH-1基因3’-UTR C/T、IL-2基因exon 1, position +114 G/T和IL-2Rβ基因C/T進行RFLP的反應條件 40
Table 2. 前列腺病人與正常人CDH-1、IL-2、IL-2Rβ基因多型性基因型分佈的情形。 41
Table 3. 前列腺病人的年齡、臨床分級、病理分級和賀爾蒙治療反應與CDH-1 C/T基因型的分佈情形。 42
Table 4. 前列腺病人的年齡、臨床分級、病理分級和賀爾蒙治療反應與IL-2 G/T基因型的分佈情形。 43
Figure 1. CDH-1 3’-UTR C/T定序的結果。(a)箭頭的位置表示並序的結果為C/T (b)箭頭的位置表示並序的結果為C (c)箭頭的位置表示並序的結果為T 44
Figure 2. CDH-1 3’-UTR C/T基因經PCR放大後的片段利用限制酶Pml I作用後所得的電泳圖。 45
Figure 3. IL-2 T/G基因經PCR放大後的片段利用限制酶Mwo I作用後所得的電泳圖。 46
Figure 4. IL-2Rβ C/T基因經PCR放大後的片段利用限制酶Hae III作用後所得的電泳圖。 47
Figure 5. 利用Kapalan-Meier存活曲線分析前列腺癌病人的存活率與IL-2（figure 1a, Log rank test, p=0.310）、IL-2Rβ（figure 1b, Log rank test, p=0.915）基因多型性的關係。 48

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