CC趨化因子配體 5及其受體之基因多型性與 口腔癌臨床病理發展風險的探討

Effect of CC chemokine ligand 5 and its receptor genes polymorphisms on the risk and clinicopathological development of oral cancer

10.6834/CSMU.2011.00106

黃妍綸

CC趨化因子配體 5 ； CC chemokine ligand 5

中山醫學大學生化暨生物科技研究所學位論文

2011年

碩士

張雲菁

繁體中文

趨化因子及其受體在發炎過程扮演一個重要的角色，且在腫瘤的發展過程也被認為是一個重要的因素。過去研究發現CC 趨化因子的配體 5(CC chemokine ligand 5; CCL5) 和其受體5 (chemokine receptor 5; CCR5) 與口腔癌的發展及其預後有很大的相關性。但是， CCL5和CCR5基因的單核苷酸多型性(SNPs)和罹患口腔癌的風險和口腔癌的臨床病理特徵的相關因可能性仍不清楚。因此，在本研究中共收集600名病例，包括253名口腔癌患者和347名正常對照組。利用聚合酶鏈反應限制片段長度多型性 (PCR-RFLP) 的分析方式，觀察CCL5- 28，CCL5-403和CCR5 - 59029三個基因多型性與口腔癌的相關性。結果發現當個體帶有CCL5-28 CG、GG或CCL5-403 TT等基因型有較高罹患口腔癌的機率，而合併CCL5-28 CG/CCL5-403CT或TT也有同樣的結果。此外在口腔癌的分化方面，發現口腔癌患者帶有CCL5 - 28 CG/CCL5-403 TT基因型較不容易發展為中度或較差分化的狀態。因此，本研究發現CCL5- 28和CCL5-403基因增加口腔癌的風險，但CCL5 - 28 CG/CCL5-403 TT基因型卻降低口腔癌的臨床病理發展。

Inflammation can be induced by cytokines, chemokines, and their receptors, and it is believed to be a risk factor on tumor initiation and progression. The contribution of CC chemokine ligand 5 (CCL5) and CC chemokine receptor 5 (CCR5) on the risk and prognosis of oral cancer is still poorly investigated. The aims of this study were to investigate the impacts of single nucleotide polymorphisms (SNPs) in CCL5 and CCR5 genes and the synergistic effects of these SNPs on the risk and clinicopathological characteristics of oral cancer. In this case-control study, a total of 253 oral cancer patients and 347 controls were recruited. The genetic polymorphisms of CCL5-28, -403 and CCR5-59029 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping analysis. The results of statistical analysis showed that the subjects with CCL5-28 CG, CCL5-28 CG or GG, and CCL5-403 TT polymorphic genotype as well as the subjects with the combinations of CCL5-28 CG/-403 CT and CCL5-28 CG/-403 TT genotypes having a significant higher risk to oral cancer than those with wild-type genotypes. Moreover, the oral cancer patients with the combination of CCL5-28 CG/-403 TT genotype presented a lower risk for developing a moderately or poorly differentiated status as compared to those with the combination of CCL5-28 CC/-403 CC genotype. These results suggest that the SNPs in CCL5-28 and -403 genes could increase the risk to have oral cancer, and the combinative effect of CCL5-28 CG and -403 TT genes might also increase the oral cancer risk but reduce the clinicopathological development of oral cancer patients.