RECK基因多型性及環境因子對口腔癌易感性及臨床病理特性之影響

在台灣地區，口腔癌 (oral cancer) 為男性排名第四好發之癌症，其發生與環境致癌因子-如檳榔、煙、酒等有關。Reversion-inducing- cysteine-rich protein with Kazal motifs (簡稱RECK) 基因會藉由與細胞外間質 (extracellular matrix) 之作用而抑制腫瘤血管新生(angiogenesis)及腫瘤侵襲(invasion) 的反應。RECK基因在許多人類癌症中已被證實有負調控 (down-regulation) 現象，且與臨床中出現的淋巴結轉移有關。在此醫院進行的病例對照分析研究中，收集了 341 位男性口腔癌患者及 415 位非癌症對照組，將其人口特性資料、RECK之基因多型性及臨床病理資料做一探討。此次研究結果顯示RECK 基因之單核苷酸多型性 rs10814325、rs16932912、rs11788747 和 rs10972727 與口腔癌的易感性無關。但於 488 位吸菸者中，具有至少一個突變核苷酸的 RECK基因並嚼食檳榔者相較正常基因且無嚼食檳榔者具有7.62倍 (95% 信賴區間 2.96-19.64) 至25.33倍 (95% 信賴區間 9.57-67.02)的機會得到口腔癌。而在 352 位嚼食檳榔者中，具有至少一個突變核苷酸的 RECK基因並且抽菸者相較正常基因且不抽菸者具有6.68倍(95%信賴區間 1.21-36.93)至18.57倍 (95%信賴區間 3.80-90.80)的機會罹患口腔癌。最後，我們分析RECK基因多型性與口腔癌患者其臨床病理特徵的相關性。結果發現，在 263 位嚼食檳榔之口腔癌患者中，在 RECK 基因多型性 rs10814325 者，具有至少一個突變核苷酸的 RECK 基因相較正常基因者有 2.26 倍 (95%信賴區間1.19-4.29) 之機會出現頸部淋巴結轉移。由這些結果顯示: 在 RECK 之基因多型性與抽菸、檳榔間存在著基因與環境間之相互作用，可能進而改變了口腔癌之易感性或使口腔癌腫瘤更容易局部轉移。

Oral cancer is the fourth common male cancer and causally associated with environmental carcinogens in Taiwan. The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) has a significant effect on tumorigenesis by limiting angiogenesis and invasion of tumors through the extracellular matrix. RECK downregulation has been confirmed in many human cancers and associated with lymph node metastasis clinically. In the present hospital-based case-controlled study, the demographic, RECK genotype and clinicopathologic data from 341 male oral cancer patients and 415 cancer-free controls were investigated. We found that RECK rs10814325, rs16932912, rs11788747 or rs10972727 polymorphisms were not associated with oral cancer susceptibility. Among 488 smokers, RECK polymorphisms carriers with betel quid chewing have a 7.62-fold [95% confidence interval (CI), 2.96-19.64] to 25.33-fold (95% CI, 9.57- 67.02) risk to have oral cancer compared with RECK wild-type carrier without betel quid chewing. Among 352 betel quid chewers, RECK polymorphisms carriers with smoking have a 6.68-fold (95% CI, 1.21-36.93) to 18.57-fold (95% CI, 3.80-90.80) risk to have oral cancer compared with those who carried wild-type without smoking. In 263 betel quid chewing oral cancer patients, RECK rs10814325 polymorphism have a 2.26-fold (95% CI, 1.19-4.29) risk to have neck lymph node metastasis compared with RECK wild-type carrier. These results support that gene-environment interactions between the RECK polymorphisms, smoking and betel quid may alter oral cancer susceptibility and metastasis.