MACC1基因多型性與環境因子對台灣口腔癌風險之影響

Effect of MACC1 genetic polymorphisms and environmental factors on the risk of Oral Cancer in Taiwan

吳思緯(Ssu-Wei Wu)

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： MACC1 (Metastasis-Associated in Colon Cancer 1)最初因被證實與大腸癌轉移有關而被命名，主要功能為調控HGF (Hepatocyte Growth Factor)/Met (Mesenchymal-epithelial transition)訊號傳遞路徑，在腫瘤增生、遷徙、侵犯、血管新生及轉移扮演重要角色，MACC1已被視為一種血清腫瘤標記，近年許多研究發現MACC1的表現量與大腸直腸癌、肝癌、肺癌、胃癌、乳癌等癌症之存活率有關，但MACC1表現與口腔癌相關性、MACC1基因多型性與環境因子對口腔癌易感性及其與臨床病理特徵之間的關聯性仍不清楚。
方法與材料：本研究以即時定量聚合酶連鎖反應 (real-time polymerase chain)於 911位口腔癌患者與1200位健康對照組中，分析5個MACC1 SNP與環境因子對罹患口腔癌風險的影響，以及各個SNP的基因型與臨床病理特徵之相關性。
結果與討論： MACC1 rs4721888基因多型性與嚼檳榔習慣會共同增加口腔癌的易感受性；MACC1 rs975263基因多型性會增加嚼檳榔口腔癌患者的頸部淋巴結及遠端轉移的風險。未來或許MACC1 rs4721888單一核苷酸多型性可以當作預測口腔癌的基因標記，而MACC1 rs975263可以作為口腔癌患者的預後指標。

關鍵字

口腔癌 ； 基因多型性 ； MACC1

並列摘要

Objective：Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, the fourth most common cancer among men, and the fifth leading cause of cancer deaths in Taiwan. Alcohol consumption, tobacco smoking, and betel quid chewing are the main known environmental risk factors of oral cancer. MACC1 (Metastasis-Associated in Colon Cancer 1), a novel identified oncogene and a key regulator of the HGF/Met signal pathway, has been demonstrated that plays an crucial role in malignant progression of many cancer, including colorectal, gastric, hepatic, pancreatic, lung, breast, esophageal cacner and head & neck cancer. The overexpression of MACC1 not only lead to abnormal activation of the HGF/Met signal pathway and promotes cell proliferation, migration, tumor invasion, angiogenesis and metastasis but has been regarded as a novel tumor marker in recent years. However, the association between MACC1 and oral cancer, the combined effect of MACC1 genetic polymorphisms and environmental carcinogens on oral cancer susceptibility and clinicopathologic features remain poorly investigated.
Methods and Materials：In the present study, we selected 5 SNPs of the MACC1 and used real-time polymerase chain reaction to analyze these SNPs in 911 oral cancer patients and 1200 cancer-free controls with environmental risk factors to oral cancer susceptibility. Furthermore, we investigated the association of SNPs genotype frequency with the clinicopathological characteristics of oral cancer patients. This is the first study which focuses on the role of MACC1 genetic polypmorphisms of oral cancer risk in Taiwanese.
Results and Discussion：Our result suggested that the combination of the MACC1 rs4721888 polymorphism with betel nut chewing increased oral cancer susceptibility. Furthermore, we observed an interaction between the MACC1 rs975263 polymorphism and clinicopathological parameters. Betel quid users in oral cancer bearing the variant genotypes of MACC1 rs975263 were shown to be more likely to develop tumors with lymph node and distant metastasis. MACC1 rs4721888 SNP may be a useful genetic marker in oral oncology for cancer prevention and early cancer detection in the future. In addition, MACC1 rs975263 SNP may be a helpful predictor in progression and outcome of oral cancer.

並列關鍵字

oral cancer ； single nucleotide polymorphism ； MACC1

參考文獻

1. Chiang CJ, Lo WC, Yang YW, You SL, Chen CJ, Lai MS. Incidence and survival of adult cancer patients in Taiwan, 2002-2012. Journal of the Formosan Medical Association = Taiwan yi zhi. 2016;115(12):1076-88.

2. Haddad RI, Shin DM. Recent advances in head and neck cancer. The New England journal of medicine. 2008;359(11):1143-54.

3. Current trends in oral cancer: a systematic review. Cancer Cell & Microenvironment. 2016.

4. Scully C, Bagan J. Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications. Oral diseases. 2009;15(6):388-99.

5. Amar A, Rapoport A, Curioni OA, Dedivitis RA, Cernea CR, Brandao LG. Prognostic value of regional metastasis in squamous cell carcinoma of the tongue and floor of mouth. Brazilian journal of otorhinolaryngology. 2013;79(6):734-7.