Fas -670A/G與Fas ligand -844C/T基因多型性與口腔鱗狀上皮細胞癌之相關性研究

Polymorphisms of Fas -670A/G and Fas ligand -844C/T and Risk of Oral Squamous Cell Carcinoma

丁鑠鈞(Shuo-Chun Ting)

指導教授 ： 林英助

高雄醫學大學/口腔醫學院/口腔衛生科學研究所碩士在職專班/碩士(2007年)

摘要

研究背景： Fas 與 Fas Ligand (FasL) 是細胞凋亡的重要調控因子，免疫系統藉由細胞凋亡來維持體內細胞正常與平衡；癌症的發生與細胞逃避免疫監控，抑制細胞凋亡作用關係密切。目前已知有些腫瘤細胞會大量表現FasL，進而與免疫細胞的Fas結合，促使免疫細胞凋亡，使得癌症得以形成。已知Fas -670A/G 與 FasL -844C/T基因多型性與蛋白質表現量有關，但與口腔癌的相關研究並不多，因此我們想探討 Fas -670A/G 與 FasL -844C/T 基因多型性與口腔癌的相關性。
研究方法：口腔鱗狀上皮細胞癌（OSCC）的患者經由高醫口腔外科與病理切片確認診斷後，邀請這些患者參加調查，經簽署人體試驗同意書後，抽取血液萃取 DNA 與完成問卷調查獲得相關資料；對照組則是高雄縣某社區居民在健康檢查後經口腔檢查，無任何明顯口腔病變、組織發炎且無任何慢性疾病的人，以同樣的問題與樣本收集方式來進行收集。針對Fas-670A/G 與 FasL-844C/T 二個位置的基因多型性進行 PCR-RFLP 實驗，實驗結果以統計方法分析其相關性。
結果： Fas 與FasL 基因多型性分佈頻率在二組研究對象中並沒有顯著不同，在OSCC患者有較高比例的人有抽菸、喝酒、嚼食檳榔的習慣。Fas -670A/G和FasL -844 C/T基因多型性在OSCC與對照組間的頻率分佈並未達到統計上顯著相關。當進行物質使用習慣的分層分析，Fas -670A/G 與FasL-844C/T 基因多型性與OSCC的相關性仍然未達統計上顯著相關，但可以觀察到抽菸習慣對OSCC的危險比（OR）在研究對象攜帶Fas -670G/G 基因型時是8.68（95% CI＝1.26∼67.16）；攜帶 -670A/G基因型時OR值是3.43（95%CI＝1.48∼7.71），但攜帶 -670A/A基因型時OR值是6.39, 95%CI＝2.21∼18.33）。然而嚼食檳榔習慣對OSCC的OR值，在研究對象攜帶Fas -670G/G 基因型時是37.25（95%CI＝6.72∼317.48）；攜帶-670A/G 基因型OR值是19.27（95%CI＝8.41∼47.61），攜帶-670A/A基因型時OR值是8.60 （95%CI＝2.83∼27.09）。抽菸習慣對OSCC的OR值在研究對象攜帶FasL -844CT基因型時是3.40（95%CI＝1.17∼9.53），但在攜帶-844C/C基因型時OR值是5.91（95%CI＝2.68∼12.91）。嚼食檳榔習慣對OSCC的OR值，在研究對象攜帶FasL -844C/T基因型時是21.80 （95%CI＝8.50∼61.45），研究對象攜帶-844C/C基因型時OR值是12.45（95%CI＝5.28∼31.04），但在飲酒習慣則未達到統計上顯著。
結論： 研究結果發現 Fas -670A/G 與 FasL -844C/T基因多型性與口腔鱗狀上皮細胞癌沒有達統計上相關性。菸、酒、檳榔是口腔癌重要的危險因子，同時菸、酒、檳榔的使用習慣對OSCC的危險性，會受到Fas 基因在-670位置與FasL基因在-844C/T位置的基因多型性的影響，未來可能提供抽菸與嚼食檳榔在致癌化過程的不同思考方向。

關鍵字

口腔鱗狀上皮細胞癌 ； 細胞凋亡 ； 單一核苷酸基因多型性

並列摘要

Background
Fas and Fas ligand (FasL) play an important role in regulating extrinsic apoptosis. Many studies reported that high levels of FasL and low levels of Fas were displayed in the cell surface of cancer tissues to escape the control of immune surveillance. Polymorphisms of Fas -670A/G and FasL -844C/T were recognized to be associated with gene expression levels in vitro study. However, the effects of functional polymorphisms of Fas -670A/G and FasL -844C/T on oral squamous cell carcinoma (OSCC) are unknown. Our aim was to determine the association between polymorphisms of Fas - 670A/G and FasL -844C/T and OSCC.

Material and methods
A total of 267 OSCC patient were recruited from Kaohsiung Medical University hospital diagnosed by dental physicians and proved by the histological examination. A total of 268 Healthy controls were recruited from a community at Kaohsiung county for health survey and oral health examination. Those people with chronic diseases, cancer histories and oral inflammation or any oral lesions were excluded from the present study. After the inform consent, we collect 10 ml peripheral blood for DNA extraction. A standardized questionnaire was applied to collect personal information, and details about the substances’ usage. Polymorphisms of Fas-670A/G and FasL-844C/T were determined by the PCR-RFLP experiments. After the data combination, statistical analysis was used to detect the associations between genetic polymorphisms and OSCC.
Result
No differenences in the frequency distributions of Fas -670A/G and FasL-844 C/T polymorphisms were found between OSCC patients and healthy controls. OSCC patients had higher prevalence of cigarette smoking, alcohol drinking, and betel quid chewing than the controls had. By stratification analysis for the participants with and without substances’ usage, Fas -670A/G and FasL -844C/T polymorphisms were not associated with the OSCC risk. Even to adjust the possible confounding variables, we didn’t find the association between Fas -670A/G and FasL-844 C/T polymorphisms and OSCC. Further to stratify the participants with -670G/G, A/G and A/A genotypes, the risks of cigarette smoking for OSCC were 8.68 (95% CI =1.26- 67.16), 3.43 (95%CI =1.48- 7.71), and 6.39 (95%CI =2.21- 18.33), respectively. By -670G/G, A/G and A/A genotypes, the risks of betel quid chewing for OSCC were 37.25 (95%CI =6.72- 317.48), 19.27 (95%CI =8.41- 47.61), and 8.60 (95%CI =2.83- 27.09), respectively. By the -844C/C, C/T, and T/T genotypes, the risks of cigarette smoking for OSCC were 5.91 (95%CI = 2.68-12.91), 3.40 (95%CI =1.17- 9.53), and 8.75 (95%CI =0.25- 417.41), respectively. By the -844C/C, C/T, and T/T genotypes, the risks of betel quid chewing for OSCC were 12.45 (95%CI = 5.28-31.04), 21.80 (95%CI =8.50- 61.45), and 761486.34 , respectively.
Conclusion
We suggest that polymorphisms of Fas-670A/G and FasL -844 C/T were not risk factors for OSCC. The habits of cigarette smoking, alcohol drinking, betel quid chewing were important risk factors for OSCC. The risks of cigarette smoking, alcohol drinking, betel quid chewing to OSCC could be differentiated by the polymorphisms of Fas -670A/G and FasL -844C/T.

並列關鍵字

Oral squamous cell carcinoma ( OSCC), Apoptosis ； Fas ； Fas ligand ； Single nucleotide polymorphisms (SNPs)

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