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  • 學位論文

探討台灣地區子宮頸腫瘤易感性和其臨床病理特徵與單核細胞趨化蛋白1和其受體趨化因子接受體2的單核苷酸多型性的相關性

Relationships of Single Nucleotide Polymorphisms of Monocyte Chemoattractant Protein 1 and Chemokine Receptor 2 with Susceptibility and Clinicopathologic Characteristics of Neoplasia of Uterine Cervix in Taiwan

指導教授 : 林隆堯 王博輝

摘要


研究目的:文獻上,很少研究探討單核細胞趨化蛋白1(monocyte chemoattractant protein 1;MCP-1)和趨化因子接受體2(chemokine receptor 2;CCR-2)的單核苷酸多型性(single nucleotide polymorphisms;SNPs)在人類子宮頸癌的臨床重要性。我們假設MCP-1和CCR-2的SNPs會影響這些基因和蛋白的表達,進而與人類子宮頸癌的致病過程有關。 研究方法及資料:我們納入86個侵入性子宮頸癌及61個高度子宮頸上皮內腫瘤的患者為研究組,和253個正常無子宮頸病變的婦女當對照組。使用聚合酶連鎖反應-限制片段長度多型性(Polymerase Chain Reaction-Restriction Fragment Length Polymorphism;PCR-RFLP)方法來偵測一個 MCP-1 SNP rs1024611 (–2518G/A) 和一個CCR-2 SNP rs1799864 (190G/A; V64I),探討與子宮頸癌臨床表徵的相關性。 研究結果:相較於在MCP-1 SNP的GG同型合子婦女,婦女帶有MCP-1 SNP GA或AA,有2.01勝算比(odds ratio;OR)發生子宮頸侵入性癌。然而,在CCR-2 SNP 兩組並無顯示差異。進一步分析顯示,相較於MCP-1 SNP野生型GG或異型合子GA的子宮頸癌婦女,帶有MCP-1 SNP同型合子AA突變的子宮頸癌婦女,有增加深層基質受侵犯(deep stromal invasion),較大腫瘤,及子宮頸旁組織侵犯(parametrium invasion)的風險。然而,在CCR-2 SNP同型合子AA突變的子宮頸癌婦女,並沒有發現有增加這些不良臨床病理表徵的風險。 結論與建議:對於台灣子宮頸癌婦女,MCP-1 SNP可能和子宮頸癌的形成有關,包括增加深層基質受侵犯,較大腫瘤,及子宮頸旁組織侵犯的風險。然而,MCP-1的接受體CCR-2的SNP,則與子宮頸癌無關連,但與癌症復發及存活率無相關性。

並列摘要


Objective:Few studies reported the implication of single nucleotide polymorphisms (SNPs) of monocyte chemoattractant protein 1 (MCP-1) and its receptor chemokine receptor 2 (CCR-2) in clinical significance of cancer of uterine cervix. We hypothesized that SNPs of MCP-1 and CCR-2 may affect the expression of these genes and then proteins. Therefore, we investigated the influence of the gene polymorphisms of MCP-1 and CCR-2 on the susceptibility and clinicopathologic characteristics of cervical neoplasia in Taiwan. Methods and Materials:We recruited 86 patients with invasive cancer and 61 with high grade squamous intraepithelial lesion and 253 control women and selected 1 MCP-1 SNP rs1024611 (–2518G/A) and 1 CCR-2 SNP rs1799864 (190G/A; V64I) to determine their genotypes distribution using polymerase chain reaction-restriction fragment length polymorphism. Results:In comparison to individuals with homozygotes GG in MCP-2 SNP, women with GA or AA carry a 2.01 odds ratio of developing cervical cancer. Nevertheless, it has been not demonstrated in CCR-2 SNP. Furthermore, women with mutant homozygote (AA) of MCP-1 SNP increase the risk of deep stromal invasion, large tumor dimension, and parametrium invasion of cervical cancer, when compared to those with wild homozygote GG or heterozygote GA. However, women with mutant homozygotes (AA) of CCR-2 SNP do not increase the risk of poor clinicopathologic characteristics. Conclusion and Suggestion:In conclusion, MCP-1 SNP may be correlated with the development, deep stromal invasion, large tumor dimension, and parametrium invasion of cervical cancer in Taiwan women patients with cancer. However, the SNP of its receptor, CCR-2, is not implicated in cervical cancer.

參考文獻


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