人類白血球抗原DQA1, DQB1與台灣口腔癌相關性之研究

Association between HLA DQA1, DQB1 and Oral Cancer in Taiwan

蔡聖健(Sheng-Chien Tsai)

指導教授 ： 陳百薫

高雄醫學大學/醫學院/醫學研究所/碩士(2008年)

摘要

口腔癌的發生率及死亡率在台灣有逐年增加的趨勢。這十餘年來國內嚼食檳榔的人數上升快速，據估計在台灣約200∼280萬人有嚼食檳榔的習慣。嚼食檳榔是造成國人罹患口腔黏膜下纖維化、口腔白斑與口腔癌的主因。嚼食檳榔會增加罹患口腔癌的風險，但並不是每個嚼檳榔的人都一定會罹患口腔癌。口腔癌與嚼食檳榔有很大相關性，卻有長期嚼食檳榔但未發展成口腔癌的案例，或是未嚼食檳榔卻發生口腔癌的病患，因此嚼食檳榔是致癌因子依舊未明。這樣的差異表現應是基因的調控所致。過去文獻指出HLA-class11與癌症者上皮細胞的抗原呈現有關，或是只探討口腔癌與HLA-class I之A、B、C部分。針對HLA-DQA1及DQB1與口腔癌關係的文獻仍甚缺乏，因此本研究即擬探討在台灣口腔癌與人類白血球組織抗原DQA1, DQB1之關係。
材料與方法：本研究利用聚合酶連鎖合成反應合併序列特異性引子(PCR-SSP)之方法來分析134位口腔癌患者以及268位正常人，其中134位患者依病灶部位再分為口腔、舌頭、頰部三群。口腔癌患者95.5%有嚼食檳榔歷史。所有研究之對象均為居住在台灣的漢人。吾人比較「人類淋巴球組織抗原」第二類抗原HLA-DQA1， -DQB1之對偶基因出現的頻率，並比較其差異在統計學上之意義。結果發現台灣口腔癌者無論分別在口腔、舌頭、頰部及整個口腔癌群DQA1,DQA1對偶基因出現的頻率均與正常人者無統計學上有意義之差異。但吾人發現HLA-class II 中單倍體 DQA*0103-DQB1*0601及DQA1*0501-DQB1*0201對口腔癌者為保護性對偶基因。結論：吾人研究顯示在口腔癌的病理成因上單倍體HLA-DQA1*0103-DQB1*0601及DQA1*0501-DQB1-0201可能扮演某些角色。

關鍵字

口腔癌 ； 感受性對偶基因 ； 保護性對偶基因 ； 人類白血球抗原 ； 單倍體 ； 聚合酶連鎖合成反應合併序列特異性引子

並列摘要

In Taiwan, the incidence of oral cancer increase every year. In recent decade, the number of chewing betel nut increase also. It was estimated that the number of chewing betel was about 2.0 to 2.8 million. Betel chewing is the main cause of submucosa fibrosis, leukoplakia and oral cancer. Not everyone chewing betel nut suffered from oral cancer. There was someone with long term betel nut chewing did not have oral cancer. There still remains controversy of betel nut chewing causing oral cancer and the difference may come from genetic origin. In the past time, there were only few papers concerning about the relationship between oral cancer and HLA class I A, B, C. and very few papers concerning about the relationship between oral cancer and HLA class II DQA1, DQB1. For further characterize the association between HLA DQA1, DQB1 and oral cancer in Taiwan, we investigated 134 Chinese oral cancer patients and 268 normal Chinese adults from Division of Surgical Oncology, Department of Surgery, Kaohsiung Medical University Hospital by using PCR-SSP (polymerase chain reaction-sequence specific primer). For 134 oral cancer patients, the male to female ratio is 34:1. 95.5% of all patients had history of betel nut chewing and all of the participants were Chinese living in Taiwan. We divided oral cancer patients into three mouth, tongue and cheek groups according to location. We found that there was no significant difference of HLA DQA1, DQB1 allele frequencies between oral cancer patients and normal adults for mouth, tongue and cheek, respectively and total oral cancer group. We observed a significantly decreased frequency of haplotype HLA DQA1*0103-DQB1*0601 and DQA1*0501-DQB1*0201 in our patients. From our data we suggests that HLA haplotype DQA1*0103-DQB1*0601 and DQA1*0501-DQB1*0201 may play some role in the pathogenesis of oral cancer.

並列關鍵字

oral cancer ； susceptible gene ； protective gene ； human leukocyte antigen ； haplotype ； polymerase chain reaction- sequence specific primer

參考文獻

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