台灣上泌尿道泌尿上皮癌的特色

The Characteristics of Upper Urinary Tract Urothelial Carcinoma in Taiwan

台灣的上泌尿道泌尿上皮癌發生率為全世界最高，且近年仍居高不下。這是一個非常重要的公共衛生議題，值得台灣醫師們持續的關注。從泌尿科醫師的角度出發，我們發現台灣上泌尿道泌尿上皮癌有以下幾個特點：腎功能異常、女性居多與中藥服用史。分子生物學研究更顯示，台灣的上泌尿道泌尿上皮癌病人身上帶有馬兜鈴酸代謝產物的印記（馬兜鈴酸DNA加合物），他們的腫瘤基因突變型態上呈現與眾不同的AT轉置現象，這現象正是馬兜鈴酸專一的突變型態。因此，我們得知至少有三成的台灣病人導因於馬兜鈴酸的暴露。此外，我們也發現相較於其他病人，馬兜鈴酸引起的病人容易有對倒復發的結果。據此，我們可以藉由檢定馬兜鈴酸，擬定專一（個人化）的治療策略。

The incidence of upper urinary tract urothelial carcinoma (UTUC) in Taiwan is the highest in the world. It is an important public health issue which is worthy of identifying the etiologies from the known evidence and analyzing the characteristics of UTUCs in Taiwan. Our clinical cohort disclosed that UTUCs in Taiwan had several characteristics, such as renal dysfunction, female dominance, and herbal usage. The following molecular biological studies revealed metabolites of aristolochic acid (AA), arsitolactam-DNA adducts, could be identified in 60% of patients' renal cortex, proving that our patients were widely exposed to AA. In addition, AA-related signature mutation pattern, A:T to T:A transversion, was observed in more than half of total mutations in UTUC tumors, suggesting that AA may cause UTUC. Therefore, we inferred that at least 30% of UTUCs in Taiwan are caused by AA. By detecting aristolactam-DNA adducts from renal cortex and signature mutations from UTUC tumors, we could definitely diagnose AA-related UTUCs. Observational studies showed a high risk of contralateral UTUC recurrence, but not bladder recurrence, in AA-related UTUC patients. Therefore, we should make a new strategy to diagnose and treat AA-related UTUC patients to improve their outcomes.