瘦體素及瘦體素受體之基因多型性與口腔癌之相關性探討

在台灣，口腔癌排在十大癌症死因第五位，且是常見的頭頸癌疾病之一，原發腫瘤失去控制及淋巴結的轉移是口腔癌病人死亡的主因，而抽菸、喝酒及檳榔則是常見的口腔癌危險因子。瘦體素 (leptin) 是脂肪細胞所分泌的一種荷爾蒙，在正常功能上，可以調控能量的平衡與免疫反應，在癌症中，則會促進癌細胞的生長、血管新生及轉移。此外，leptin會跟膜上的瘦體素受體 (leptin receptor) 結合，活化下游訊息傳遞路徑來調控癌症相關基因的表現。在乳癌的研究中，leptin (LEP)及leptin receptor (LEPR)被發現會在癌症病人中大量表現。基因多型性 (gene polymorphism) 是指基因的變化在一個族群中大於1%，其中以單一核苷酸的多型性 (single nucleotide polymorphism; SNP) 最常見，在癌症研究中，許多基因多型性都被報導與口腔癌及其臨床表徵有關，但有關leptin及leptin receptor基因多型性在口腔癌的研究卻很少被提到，因此本篇研究利用567個口腔癌患者和560個正常人的DNA來探討LEP -2548 G/A (rs7799039)、LEPR K109R (rs1137100) 和LEPR Q223R (rs1137101) SNPs與環境危險因子的交互作用對口腔癌風險的影響。結果顯示，帶有LEP -2548 G/A基因多性型的口腔癌病人相對於帶有A/A基因型的口腔癌病人有較低的風險發展成晚期的臨床分期。此外，LEP -2548 G/A基因型對無抽菸族群的口腔癌發生的影響高於有抽菸族群。本篇研究證實LEP -2548 G/A (rs7799039)、LEPR K109R (rs1137100) 和LEPR Q223R (rs1137101) 的基因多型性與口腔癌的易感性無關;帶有LEP -2548 G/A基因多型性的口腔癌患者會有較低的臨床分期風險;帶有LEP -2548 G/A基因多型性且無抽癌的族群可能會增加罹患口腔癌的風險。

Oral cancer is causally associated with environmental carcinogens, and the susceptibility to carcinogen-mediated tumorigenesis is proposed to be genotype-dependent. Leptin (LEP) and leptin receptor (LEPR) both play a crucial role in the mediation of physiological reactions and carcinogenesis and may serve as a candidate biomarker of oral cancer. The present case-control study aimed to examine the effects of LEP -2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) SNPs with or without interacting to environmental carcinogens on the risk for OSCC. The SNPs of three genetic allele, from 567 patients with oral cancer and 560 healthy controls in Taiwan were analyzed. The results shown that the patients with polymorphic allele of LEP -2548 have a significant low risk for the development of clinical stage (A/G, AOR = 0.670, 95% CI = 0.454–0.988, P < .05; A/G+G/G, AOR = 0.676, 95% CI = 0.467–0.978, P < .05) compared to patients with ancestral homozygous A/A genotype. Additionally, an interesting result was found that the impact of LEP -2548 G/A SNP on oral carcinogenesis in subjects without tobacco consumption is higher than subjects with tobacco consumption. These results suggest that the genetic polymorphism of LEP -2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) were not associated to the susceptibility of oral cancer; SNP in LEP -2548 G/A showed a poor clinicopathological development of oral cancer; Population without tobacco consumption and with polymorphic LEP -2548 G/A gene may significantly increase the risk to have oral cancer.