Aristolochic acid containing herbs induce gender-related oncological differences in upper tract urothelial carcinoma patients

Abstract

BackgroundIn China, upper tract urothelial carcinoma (UTUC) is less prevalent but more malignant in males. This study investigates the prognostic factors and causes of gender-based differences in Chinese populations.MethodsBetween 1999 and 2011, 687 UTUC patients who underwent surgery were utilized for this study. We evaluated the differences in oncological characteristics, epigenetic biomarkers, cancer-specific survival (CSS), bladder recurrence (BR) rate, and contralateral upper tract recurrence (CUTR) rate. Smoking history, benzene exposure history, and the history of using aristolochic acid (AA) containing herbs were analyzed in detail.ResultsCompared with male patients, female patients showed poorer renal function, lower proportions of tumor stage III/IV, and smaller tumor diameters. The CSS in male patients was lower than that in female patients. Significant gender-related differences were observed concerning various prognostic factors. In female patients, poorer survival rates were attributed to the primary tumor location in the ureter, large diameter primary tumors, severe chronic kidney disease, papillary tumor architecture, high tumor stages, positive N status, and methylated ABCC6 promoters. In male patients, older age, ipsilateral hydronephrosis, large tumor diameters, sessile tumor architecture, high tumor stages, and methylated TMEFF2 promoters were associated with higher cancer-specific mortality. AA might be the main cause of these gender-based differences. The AA-induced UTUC patients presented smaller tumor diameters, lower tumor stages, fewer positive N statuses, more multifocal tumors, lower methylation indices, and poorer renal function. Although AA-induced UTUC patients exhibited better survival rates, BR and CUTR rates were significantly worse.ConclusionIn China, there exist significant AA-induced differences between male and female UTUC patients. The bladders and contralateral upper urinary tracts of AA-induced UTUC patients should be carefully monitored after surgery.

Integration of medicinal plants into the traditional system of medicine for the treatment of cancer in Sokoto State, Nigeria

“…Generally, Aristolochia and one of its chief components aristolochic acid have been known for its carcinogenic, and nephrotoxic effects for a very long time ( Michael et al., 2009 ). Recently, several toxicological risks associated with a history of using herbal medicines containing aristolochic acid amongst cancer patients have been reported ( Aydin et al., 2017 ; Ban et al., 2018 ; Chen et al., 2018 ; Hoang et al., 2016 ; Hung et al., 2016 ; Kanaan et al., 2016 ; Popovska-Jankovic et al., 2016 ; Xiong et al., 2018 ; Zhong et al., 2017 ). Despite the reported cases on the use of herbs containing aristolochic acid around the world, a similar effect associated with the use of Aristolochia spp has yet to be reported in Nigeria.…”

Propensity-Matched Survival Analysis of Upper Urinary Tract Urothelial Carcinomas between End-Stage Renal Disease with and without Kidney Transplantation

“…In recent reports, relatively high prevalence of UTUC with aristolochic acid (AA) mutational signatures was found in Taiwan [6, 7]. Aristolochic acid-related UTUC is associated with a specific oncologic pattern [8], namely, aristolochic acid nephropathy, which is a toxic interstitial nephropathy caused by ingestion of plants containing aristolochic acids (AA) as part of traditional phytotherapies (formerly known as Chinese herb nephropathy) [9]. There is relatively high prevalence of UTUC and subsequent bladder cancer for such patients with AA-related nephropathy after KT [10].…”

Prognostic role of stromal tumor-infiltrating lymphocytes in locally advanced upper tract urothelial carcinoma: A retrospective multicenter study (TSU-02 study)

“…2 Distinct from non-AA UTUC, AA-related UTUC exhibits unique clinicopathologic features, such as prevalence in females, multifocality, and lower T stage, as demonstrated in both the present study and our previous reports. 36,37 AA-related UTUC with unique underlying pathogenesis may have distinct profiles of prognosis and therapeutic strategy. As previously reported, increased gene mutational burden and neoantigen load were observed in patients with AA exposure, 38,39 which can be recognized by T cells and generate antibodies.…”