檳榔所引起口腔癌之染色體變異的研究

Chromosome Changes Diagnosed in Betel-Quid-Associated Oral Cancer in Taiwan

王博正(Bor-Jeng Wang)

指導教授 ： 周明智

中山醫學大學/醫學院/醫學研究所/碩士(2006年)

摘要

背景及目的
在台灣未有人以傳統的細胞遺傳學方法G-banding及頻譜式染色體分析法(SKY)來研究這些因嚼食檳榔所引發口腔癌細胞之染色體變異。在本文收集92位因嚼食檳榔而得口腔癌之病人，分析他們染色體的變異與國外因嚼食煙草及抽煙引起口腔癌病人的染色體變異作一比較。
材料及方法
在2001-2002年之中，收集92個口腔癌病人組織，這些腫瘤切塊在組織培養之前先切成小碎片，經以酵素collagenase及dispaseII處理後放入Bio-MAX之組織培養液培養。借由傳統的G-banding method及使用頻譜式染色體分析法(SKY)探討口腔癌細胞之染色體變異。
結果
不正常的染色體反復地出現在某些特定的染色體，尤其是Y 染色體丟失(loss of Y chromosome)、4號染色體整條染色體丟失或長臂部份不見了、8號染色體的長臂同質化 [i(8q)]及17號染色體整條染色體丟失或短臂部份不見了。與國外因嚼食煙草及抽煙引起口腔癌病人的染色體變異比較結果，並無明顯差異。
結論
1.在本研究發現嚼食檳榔所引發口腔癌染色體的變異，基本上與在2006年發表的106個與煙草有關的口腔癌染色體變異很類似。顯示口腔癌變是與染色體的變異有關，與刺激源的種類無關。
2.本研究發現4號染色體短臂丟失、8號及17號染色體長臂增長及長臂同質化(isochromosome formation for the long arm)都與抑癌基因消失有關，會增加癌變之機會。
3.雖然Y染色體的消失有年齡因素的影響，但我們卻也發現口腔癌病人Y染色體的消失，似乎反眏出病理性結果的傾向。

關鍵字

檳榔 ； 口腔癌 ； 染色體變異

並列摘要

Background and Purpose: Oral cancer is the 4th leading cause of death in males in Taiwan. Studies of epidemiological aspects, chromosomal changes by CGH analysis and mitochondrial DNA alterations have been pursued, but detection of chromosomal changes by the traditional cytogenetic method (G-banding) and the recently developed molecular cytogenetic method such as spectral karyotyping (SKY) has not been undertaken. In this report, we studied chromosome changes in 92 cases of oral cancer associated with betel nut-chewing by G-banding and SKY methods, and compared our findings with those associated by tobacco chewing or smoking.
Material and methods: 92 oral cancer tissue specimens were collected from the dental clinic of Changhua Christian Hospital of Taiwan during 2001-2002. The tumor mass was disaggregated into single cells or small clusters by both mechanical and enzymatic approaches before cultured in Bio-MAX. The enzyme solution used in this study was a combination of collagenase and dispase II. To investigate chromosomal changes that occurred in betel-quid associated oral cancers, we performed chromosome studies by using traditional G-banding method in conjunction with spectral karyotyping (SKY) analysis. Results: Among the 92 tissue specimens analyzed, 32 cases were found with chromosomal abnormalities, of which 13 were multiple primary oral cancers, 7 recurrent oral cancers and 12 oral cancers post radiotherapy. The abnormalities were repeatedly seen in some particular chromosomes. These included: 8 cases with loss of the Y chromosome, 3 cases with deletions in the long arm of chromosome 1, 4 cases with deletions in the long arm of chromosome 2, 4 cases with loss of the long arm of chromosome 6, 3 cases with an isochromosome for the long arm of chromosome 8, 4 cases with either loss of the whole chromosome or partial deletion of the long arm of chromosome 4, and findings of HSR on chromosome 1q, 11q and 13q. The most common gains of chromosome arms were 8q, 9q and 11q, while the frequent losses of chromosome arms were 3p and 4q. It was also interesting to note in one patient that only a normal karyotype was seen in the tumor tissue, but a karyotype with near triploidy (62-68) was observed in culture of neck metastatic lymph node. In both studies, losses of genetic material dominated over gains. However, loss of genetic material involving chromosome 17 either by loss of the whole chromosome or by loss of only the short arm was documented repeatedly in 5 cases (16%) of 32 cases with chromosome abnormalities) in our study, but not in the Lund University Hospital study
Conclusion: There were no major differences between the present study and the study reported by Jin et al.(2006). These consistent results indicated that common genetic pathways at chromosome level in terms of numerical changes and structural rearrangements such as translocation, isochromosome formation and the presence of homogeneously staining region (HSR) are involved in the initiation and progression of oral SCC irrespective of their etiological origin. Besides an aging phenomenon, loss of Y may reflect a pathogenetic consequence of cancer development in oral cancer. SKY has proven to be a powerful tool in elucidating complex chromosomal rearrangement.

並列關鍵字

Betel Quid ； Oral Cancer ； Chromosomal abnormality

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