人類乙醯轉移?基因型與腦瘤之關聯研究

The Correlation between Human N-acetyltransferase 2 Genotypes and Brain Tumors

蕭珮妤(Pei-Yu Hsiao)

指導教授 ： 李仁愛 ； 陳香吟

臺北醫學大學/藥學院/藥學研究所/碩士(2006年)

摘要

腦瘤佔臺灣地區所有癌症死亡原因之1.25%，其五年存活率僅約20%。目前有關腦瘤的成因仍未明，已確認的危險因子僅有游離輻射一項。人類第二型乙醯轉移?（NAT2）參與許多致癌物的活化或解毒過程，其代謝速率有顯著的個體差異，一般以帶有一個以上野生型對偶基因（NAT2*4）者為rapid acetylator，其餘基因型稱為slow acetylator。NAT2和許多癌症有關，但和台灣地區腦瘤的相關則尚未有研究。 本研究主要目的為探討乙醯轉移?基因型的分布在腦瘤病患與未罹患癌症之配對對照組中的差異。次要目的為分析不同乙醯轉移?基因型的腦瘤病患其存活率、腫瘤型態、腫瘤分級之差異。 本研究比較27名腦瘤病患及27名正常對照組，以PCR-RFLP方式分析病患之腫瘤切片及對照組的週邊血液檢體，檢測NAT2*5、NAT2*6及NAT2*7，共三個allele。結果發現NAT2*7 allele在腦瘤病患組的比例明顯較對照組高，p=0.001，帶有NAT2*7 allele者罹患腦瘤之odds ratio為6.79（95%, CI 2.06-22.37）；帶有NAT2*7 allele的病患中astrocytoma和glioblastoma multiforme的比例較高（p=0.016）。其他次要目的如存活、率腫瘤類型等則未發現有差異。因此，NAT2*7 allele與astrocytoma和glioblastoma multiforme之間的關聯值得進一步探討研究。

關鍵字

乙醯轉移? ； 腦瘤 ； 代謝多型性 ； 基因型 ； 危險因子 ； 人類 ； 病患組 ； 對照組 ； 臺灣

並列摘要

Brain tumors accounts for 1.25% of cancer-related death in Taiwan, and the 5-year survival is only 20%. The cause of brain tumors was not fully understood, and the only known risk factor is ionizing radiation. Previous studies have found that the highly polymorphic arylamine N-acetyltransferase 2 (NAT2) is related to many cancer development probably due to both activation and inactivation reaction of numerous carcinogens. Subjects with wild type allele NAT2*4 were called rapid acetylators, and others were called slow acetylators. The correlation of NAT2 and brain tumors in Taiwan has not yet been studied. The primary purpose of this study was to compare the distribution of acetylator types between brain tumor patients and age-matched normal subjects in Taiwan. The secondary purpose was to compare the progression-free survival, overall survival, and tumor type and grading of brain tumor patients with different acetylator types. We studied the NAT2* polymorphisms (NAT2*5, NAT2*6, NAT2*7) in 27 brain tumor tissues and 27 matched control samples from peripheral blood by the PCR-RFLP method. The allele frequency of NAT2*7 was found significantly higher in case group, p=0.001 (odds ratio 6.79, 95% CI, 2.06-22.37). The most common types of tumors for the patients with NAT2*7 were astrocytoma and glioblastoma multiforme; while those for the patients without NAT2*7 were oligodendroglioma, meningioma, and glioblastoma multiforme. No differences were found in survival or tumor grading. Further studies are warranted to clarify the relationship between NAT2*7 and occurance of astrocytoma and glioblastoma multiforme.

並列關鍵字

N-acetyltransferase ； Brain Neoplasms ； Metabolic polymorphism ； Genotype ； Risk factors ； Human ； Taiwan

參考文獻

8.行政院衛生署國民健康局. 中華民國九十一年度癌症登記報告; 2005.

2.Wrensch M, Minn Y, Chew T, Bondy M, Berger MS. Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro-oncol 2002;4(4):278-99.

3.Lin HJ, Han CY, Lin BK, Hardy S. Ethnic distribution of slow acetylator mutations in the polymorphic N-acetyltransferase (NAT2) gene. Pharmacogenetics 1994;4(3):125-34.

4.Hein DW. N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk. Oncogene 2006;25(11):1649-58.

5.Kleihues P, Louis DN, Scheithauer BW, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002;61(3):215-25; discussion 26-9.