WISP1基因多型性及環境因子對口腔癌易感性相關之探討

Impact of WISP-1 gene polymorphisms and environmental factors on oral cancer susceptibility in Taiwan.

王律堯(Lyu-Yao Wang)

指導教授 ： 楊順發

中山醫學大學/醫學院/醫學研究所/碩士(2017年)

摘要

研究目的：口腔鱗狀細胞癌 (Oral squamous cell carcinoma, OSCC)，為最常見之頭頸部癌症，佔人類惡性腫瘤 1%-2%，且有不良的預後和低生存率等特徵。WNT1-inducible signaling pathway protein 1 (WISP1) 為隸屬於 Cyr61、CTGF、Nov 等 CCN 家族之 cysteinerich的細胞外間質蛋白，其功能被認為與癌變有關。因此，本研究在探討WISP-1之單核甘酸多型性 (single-nucleotide polymorphisms, SNPs) 與口腔癌的易感性和臨床特徵的相關性。研究方法/資料：本研究收集了900名OSCC病患和1200名健康對照組，利用 Real-time 聚合酶鏈反應 (real-time polymerase chain reaction) 分析6個WISP-1的SNP位點。結果顯示帶有至少一個G-allele的WISP1 rs2929970多型性者具有較高的 OSCC 易感性。此外，與吸煙者相比，具有較高頻率的WISP1 rs2929970（AG + GG）之非吸煙者患者有較晚的臨床分期 (Stages III和IV) 以及較大的腫瘤尺寸。另外，有嚼食檳榔且帶有 WISP1 16893344 (CT+TT) 的 OSCC 病患，有較低的淋巴轉移風險。總結：此篇研究結果顯示，WISP1 rs2929970 與抽菸和 WISP1 rs16893344 與嚼食檳榔的複合結果皆會助長 OSCC 的發生。因此，WISP1基因多型性或許可作為 OSCC 的篩檢及治療標靶。

關鍵字

基因多型性 ； 口腔癌 ； WISP1基因

並列摘要

Background
Oral squamous cell carcinoma (OSCC), which is the most common head and neck cancer, accounts for 1%–2% of all human malignancies and is characterized by poor prognosis and reduced survival rates. WNT1-inducible signaling pathway protein 1 (WISP1), a cysteinerich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and may be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms (SNPs) to elucidate OSCC susceptibility and clinicopathologic characteristics.
Methodology/Principal findings：Real-time polymerase chain reaction was used to analyze 6 SNPs of WISP1 in 900 OSCC patients and 1200 cancer-free controls. The results showed that WISP1 rs2929970 polymorphism carriers with at least one G allele were susceptible to OSCC. Moreover, compared with smokers, non-smoker patients with higher frequencies of WISP1 rs2929970 (AG + GG) variants had a late stage (stages III and IV) and a large tumor size. In addition, OSCC patients who were betel quid chewers and carried WISP1 rs16893344 (CT + TT) variants had a low risk of lymph node metastasis.Conclusion：Our results demonstrate that a joint effect of WISP1 rs2929970 with smoking as well as WISP1 rs16893344 with betel nut chewing causally contributes to the occurrence of OSCC. WISP1 polymorphism may serve as a marker or a therapeutic target in OSCC.

並列關鍵字

WISP-1 gene ； polymorphisms ； oral cancer

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