胞漿素原活化因子抑制劑之基因多型性與子宮內膜癌的相關性探討

Association of plasminogen activator inhibitor gene polymorphism of endometrial cancer

蘇重光(Chung-Kuang Su)

指導教授 ： 周明智

中山醫學大學/醫學院/醫學研究所/博士(2012年)

https://doi.org/10.6834/CSMU.2012.00056

摘要

子宮內膜癌是一種常見的女性泌尿生殖道惡性腫瘤。危險因素包括可能為暴露於雌激素中。然而，癌症病變是一個複雜的過程，大多數子宮內膜癌病例無法純粹由荷爾蒙來解釋。遺傳因素將提供進一步關於子宮內膜癌的資訊，亦可瞭解此惡性腫瘤的病因和提供改進預防措施的科學依據，才能有效的預防及治療。本論文觀察尿激酶型胞漿素原活化因子(urokinase plasminogen activator; u-PA)、尿激酶型胞漿素原活化因子受體 (u-PAR)和胞漿素原活化因子的抑制劑 (PAI-1)的基因多型性位置藉由探討u-PA系統基因的基因多型性來分析子宮內膜癌與其關聯性。我們收集了134位病例組和302名對照組的血液檢體，利用聚合酶連鎖反應限制片段長度多型性分析其u-PA的rs4065 C/T、u-PAR的rs344781 T/C和 PAI-1 其rs1799889 4G/5G 的基因多型性。結果發現PAI-1 rs1799889 的4G/4G基因型和4G等位基因頻率明顯在子宮內膜癌(分別為36.6％和61.6％)和對照組 (分別為25.5％和52.2％) 之間有明顯的差異，而我們更進一步分析，結果顯示其PAI-1基因型4G/4G相對於5G/5G增加了2.26倍的罹癌率 (95% CI 1.20-4.27)。但是在u-PA的rs4065 及u-PAR的rs344781 基因多型性方面與罹患子宮內膜癌的風險並無統計學上的意義。在而我們也進一步發現PAI-1 4G/4G基因型的高罹癌風險，是出現在50歲以上的患者及罹癌之後其癌症期數為stage I, II期的族群。由本研究的結果，推論在大於50歲的子宮內膜癌患者中，諸多造成子宮內膜癌的因子中，與PAI-1的基因多型性有關，而與u-PA及u-PAR基因多型性無關。因此，希望可以將PAI-1的基因多型性應用到子宮內膜癌中，並期許可以當作一個診斷或追蹤子宮內膜癌的輔助因子。

關鍵字

子宮內膜癌 ； 尿激酶型胞漿素原活化因子

並列摘要

To investigate the association of urokinase plasminogen activator (u-PA) system genes, including u-PA, u-PA receptor (u-PAR), and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms, with risk of endometrial cancer. We enrolled a total of 134 patients with endometrial cancer confirmed by histopathology and 302 unrelated healthy individuals. Genetic polymorphisms of u-PA system genes, including u-PA rs4065 C/T SNP, u-PAR rs344781 T/C single nucleotide polymorphism (SNP) and PAI-1 rs1799889 4G/5G SNP were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping analysis. The results show that frequency of PAI-1 rs1799889 4G/4G genotype and 4G allele differed significantly between patients with endometrial cancer (36.6% and 61.6% respectively) and healthy individuals (25.5% and 52.2 % respectively). Individuals with PAI-1 rs1799889 4G/4G genotype were at higher risk of endometrial cancer (OR=2.26; 95%CI: 1.20-4.27). Stratification analysis showed individuals with PAI-1 rs1799889 4G/4G genotype were at elevated risk for endometrioid type (OR=2.49; 95% CI 1.27-4.88), low stage (stage I-II) endometrial cancer (OR=2.34; 95% CI 1.21-4.52). However, no significant differences in u-PA C/T SNP, u-PAR T/C SNP genotypes were observed between endometrial carcinoma cases and controls.

並列關鍵字

endometrial cancer ； u-PA

參考文獻

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