Departments of Pharmacological Sciences and Medicine, Stony Brook University, Stony Brook, NY, USA.
Department of Urology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100, Taiwan, ROC.
World J Urol. 2023 Apr;41(4):899-907. doi: 10.1007/s00345-022-04100-5. Epub 2022 Jul 22.
The high incidence of upper urinary tract urothelial carcinoma (UTUC) in Taiwan is largely due to exposure to aristolochic acid (AA), a principal component of Aristolochia-based herbal medicines. Here we systematically review the molecular epidemiology, clinical presentation and biomarkers associated with AA-induced UTUC.
This is a narrative review. Medline, Embase, and Web of Science were searched from inception to December 31, 2021. Studies evaluating the association, detection, and clinical characteristics of AA and UTUC were included.
A nationwide database revealed 39% of the Taiwanese population had been exposed to AA-containing herbs between 1997 and 2003. Epidemiological reports revealed AA posed a significantly higher hazard for renal failure and UTUC in herbalists and the general population who ingested AA-containing herbs. The presence of aristolactam-DNA adducts and a distinctive signature mutation, A:T to T:A transversions, located predominantly on the non-transcribed DNA strand, with a strong preference for deoxyadenosine in a consensus sequence (CAG), was observed in many UTUC patients. Clinically, AA-related UTUC patients were characterized by a younger age, female gender, impaired renal function and recurrence of contralateral UTUC. To date, there are no preventive measures, except prophylactic nephrectomy, for subjects at risk of AA nephropathy or AA-related UTUC.
AA exposure via Aristolochia-based herbal medicines is a problem throughout Taiwan, resulting in a high incidence of UTUC. Aristolactam-DNA adducts and a distinctive signature mutation, A:T to T:A transversions, can be used as biomarkers to identify AA-related UTUC. AA-related UTUC is associated with a high recurrence rate of contralateral UTUC.
台湾地区上尿路尿路上皮癌（UTUC）发病率较高，主要与摄入马兜铃酸（AA）有关，AA 是马兜铃属草药的主要成分之一。本文系统综述了与 AA 相关的 UTUC 的分子流行病学、临床表现和生物标志物。
这是一篇叙述性综述。检索了 Medline、Embase 和 Web of Science 数据库，检索时间截至 2021 年 12 月 31 日。纳入评估 AA 与 UTUC 之间关联、检测和临床特征的研究。
一项全国性数据库显示，1997 年至 2003 年期间，39%的台湾居民接触过含 AA 的草药。流行病学报告显示，草药师和摄入含 AA 草药的一般人群中，AA 显著增加了肾衰竭和 UTUC 的发病风险。在许多 UTUC 患者中观察到存在aristolactam-DNA 加合物和特征性突变，即 A:T 到 T:A 颠换，主要位于非转录 DNA 链上，在强 CAG 一致性序列中强烈偏好脱氧腺苷。临床上，AA 相关 UTUC 患者的特征为年龄较小、女性、肾功能受损和对侧 UTUC 复发。迄今为止，除预防性肾切除术外，对于有发生 AA 肾病或 AA 相关 UTUC 风险的人群，尚无其他预防措施。
台湾地区普遍存在通过马兜铃属草药摄入 AA 的问题，导致 UTUC 发病率较高。aristolactam-DNA 加合物和特征性突变 A:T 到 T:A 颠换可用作识别 AA 相关 UTUC 的生物标志物。AA 相关 UTUC 与对侧 UTUC 高复发率相关。
