楊順發Shun-Fa Yang洪晟鈞Sheng-Chun Hung醫學研究所2026-10-299999-12-3120202020-06-24https://handle.ncl.edu.tw/11296/e7zp5yhttps://scholars.csmu.edu.tw/handle/123456789/36488泌尿上皮惡性腫瘤 (Urothelial cell carcinoma, UCC) 是泌尿道最常見的惡性腫瘤之一，腫瘤的發生常跟環境暴露及基因有關。糖化終端產物受體 (Receptor for Advanced Glycosylation Endproducts, RAGE) 屬於細胞膜免疫球蛋白的一種，與體內的免疫調控有關，在慢性發炎相關疾病與腫瘤生成中扮演重要的角色。本研究的目的在於探討RAGE的基因多型性與泌尿上皮惡性腫瘤的發生及臨床病理與預後的關聯性。本篇研究共計1023名受試者，其中431名為泌尿上皮惡性腫瘤的患者，而592名為無癌症的健康對照組。RAGE基因的四個位置之多型性，包括-429T>C (rs1800625)，-374T>A (rs1800624)，Gly82Ser (rs2070600) 及1704G>T (rs184003)，使用TaqMan assay做即時聚合酶連鎖反應 (real-time polymerase chain reaction, real-time PCR) 來分析檢驗。研究發現個體於RAGE基因的rs1800625含至少一個C allele相較於野生型有更高機會罹患泌尿上皮癌 (AOR=1.9, 95% CI = 1.21-2.98, p=0.005)。於rs2070600為AA相較於野生型GG有更高的罹患泌尿上皮癌的機率 (AOR=2.26, 95% CI = 1.06-4.81, p=0.035)。次族群分析發現在年紀小於65歲的泌尿上皮癌病患，於rs1800625包含至少一個C allele有更高的機會罹患肌肉侵犯型(OR=2.63, 95%CI = 1.11-6.27, p=0.029) 及淋巴轉移 (OR=3.36, 95%CI = 1.31-8.61, p=0.012) 的機率。在中位數39個月的觀察期之後，發現於年紀小於65歲的病患，在rs184003中的TT基因型可能有更差的疾病相關存活率 (disease specific survival, HR = 7.58, 95% CI = 2.52–22.77, p< 0.001) 及總體存活率 (overall survival, HR = 6.45, 95% CI = 2.19–19.034, p< 0.001)。這是第一篇探討RAGE基因多型性與泌尿上皮腫瘤之關聯性的文章。個體於rs1800625擁有至少一個C allele有較高的罹患泌尿上皮癌的風險。此外，於年紀小於65歲的個體，若rs184003為TT基因型，有更差的疾病相關存活與整體存活率。Urothelial cell carcinoma (UCC) is a common malignancy of the urinary tract that is associated with environmental factors and genetic effects. Receptor for advanced glycosylation endproducts (RAGE) plays a vital role in chronic inflammation and tumorigenesis. This study explored the impact of RAGE gene polymorphisms on the clinicopathological status and prognosis of patients with UCC. A total of 1,023 participants, including 431 patients with UCC and 592 healthy controls, were recruited for this study. Four polymorphisms of the RAGE gene, including -429T>C (rs1800625), -374T>A (rs1800624), Gly82Ser (rs2070600), and 1704G>T (rs184003), were examined using a real-time polymerase chain reaction with the TaqMan assay. We found that individuals carrying at least 1 C allele at RAGE rs1800625 had a higher risk of developing UCC than those carrying a wild-type allele. Subgroup analysis revealed that among UCC patients aged younger than 65 years, those with a C allele at rs1800625 had a higher incidence of muscle invasive tumor and lymph node invasion. With a median follow-up of 39 months, TT polymorphisms of rs184003 were associated with worse disease-specific survival (HR = 7.58, 95% CI = 2.52−22.77, p< 0.001) and all-cause survival (HR = 6.45, 95% CI = 2.19−19.034, p< 0.001) in UCC patients aged younger than 65 years. In conclusion, this study is the first to report a correlation between RAGE polymorphisms and UCC risk. Individuals that carry at least 1 C allele at rs1800625 of RAGE are associated with a higher risk of UCC development, particularly if they belong to the categories previously identified. TT polymorphism at rs184003 is associated with worse disease-specific survival and overall survival in people aged ≦65 years.糖化終端產物受體基因多型性泌尿上皮惡性腫瘤Receptor for advanced glycosylation endproductsGene polymorphismUrothelial cell carcinomathesis