| 摘要: | Caveolin-1 (Cav-1)的功能與抑制腫瘤生長有關，在許多腫瘤生長的調控中佔有重要角色。而頭頸部惡性腫瘤是目前台灣最盛行的腫瘤之一，也是造成男性癌症死亡之第四名，本研究探討頭頸部腫瘤(口腔癌與鼻咽癌)之致病性與Cav-1基因型之關聯性。本實驗是基於醫學中心疾病與對照組之研究，關於Cav-1之基因多型性與中台灣之口腔癌及鼻咽癌之致病性之分析。共搜集620位口腔癌患者及176位鼻咽癌患者，並依年齡及性別搜集無任何癌症之健康成人為對照組。分別就每一位之以PCR-RFLP分析Cav-1基因型與導致口腔癌與鼻咽癌之關係。在口腔癌方面我們發現Cav-1 G14713A (rs3807987)以及 T29107A (rs7804372)之基因多型性與罹患口腔癌有相關性，在基因型(P=1.7*10-18 and 2.5*10-4)及對偶基因表現頻率分析(P=3.3*10-19 and 9.5*10-6)都有統計上之差異。在鼻咽癌方面，我們也發現Cav-1 T29107A (rs7804372) 之基因多型性與罹患鼻咽癌有相關性，在基因型分析(P=0.00188)及對偶基因頻率分析(P= 2.5*10-4) 也都有顯著之差異。 我們在進一步之基因配對分析中發現，Cav-1 G14713A/T29107A配對中 GG/AT 或 GG/AA之基因配對型式，相較於GG/TT， 有0.72倍相對較低之口腔癌發生率(95% confidence interval=0.52-0.99)，而其他之基因配對型式都有較GG/TT更高之罹癌率。我們發現Cav-1 (T29107A)之基因型可以作為口腔癌及鼻咽癌之共同特異性生物標記，而G14713A這個位點則可以當作口腔癌之特異性生物標記。以上發現對於口腔癌及鼻咽癌之早期診斷及疾病預測具有相當的幫助。未來我們會將這些基因型的差異與臨床的資料進行比對，以瞭解每一位病人真正的病因及適切的治療方式。
Caveolin-1, which has been proposed as a candidate tumor suppressor, plays a regulatory role in several signaling pathways. The head and neck cancers are one of most prevalent cancers and causing death of Taiwan. The aim of this study is to evaluate the association between two most serious cancers of head and neck cancer, oral cancer and nasopharyngeal carcinoma, their susceptibilities and Cav-1 genotypes. In this hospital—based case—control study, the associations of Cav-1 polymorphisms with oral cancer and nasopharyngeal carcinoma risks in a Central Taiwanese population were investigated. Six hundred patients with oral cancer, 176 nasopharyngeal carcinoma patients and age- and gender-matched healthy controls recruited were genotyped and analyzed by PCR-RFLP method. As for oral cancer, there were significant differences between oral cancer and control groups in the distributions of their genotypes (P=1.7*10-18 and 2.5*10-4) and allelic frequencies (P=3.3*10-19 and 9.5*10-6) in the Cav-1 G14713A (rs3807987) and T29107A (rs7804372) polymorphisms, respectively. As for nasopharyngeal carcinoma, There were significant differences between nasopharyngeal carcinoma and control groups in the distributions of the genotypic (P=0.00188) and allelic frequencies (P= 2.5*10-4) in the Cav-1 T29107A (rs7804372) polymorphism. We have further done the haplotype analysis for the two SNPs found significantly associated with oral cancer, those who had GG/AT or GG/AA at Cav-1 G14713A/T29107A showed a 0.72-fold (95% confidence interval=0.52-0.99) decreased risk of oral cancer compared to those with GG/TT, while those of any other combinations were of increased risk.
We have found a common SNP biomarker of Cav-1 (T29107A) for both oral cancer and nasopharyngeal carcinoma. Also there is a unique novel SNP biomarker for oral cancer susceptibility (G14713A). All these findings are very useful for early detection and prediction of oral cancer and nasopharyngeal carcinoma. In the future, the functional changes of these genotypes and the interactions of these SNPs with environmental factors, such as smoking, alcohol drinking and betel quid chewing for oral cancer, will be further analyzed. As for the clinical outcome analysis, oral cancer patients with AG or AA at Cav-1 G14713A, and NPC patients with AT or AA at Cav-1 T29107A, compared with their counterpart groups, have lower survival and higher distant metastasis rates. |
