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

Authors Xiong G, Yao L, Hong P, Yang L, Ci W, Liu L, He Q, Gong K, Li X, Zhou L

Received 29 June 2018

Accepted for publication 24 September 2018

Published 4 December 2018 Volume 2018:10 Pages 6627—6639

DOI https://doi.org/10.2147/CMAR.S178554

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo


Gengyan Xiong,1,* Lin Yao,1,* Peng Hong,1,* Li Yang,2 Weimin Ci,3 Libo Liu,1 Qun He,1 Kan Gong,1 Xuesong Li,1 Liqun Zhou1

1Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, China; 2Department of Nephrology, Peking University First Hospital, Beijing, China; 3Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China

*These authors contributed equally to this work

Background: In 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.
Methods: Between 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.
Results:
Compared 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.
Conclusion: In 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.

Keywords: upper tract urothelial carcinoma, aristolochic acid, gender difference, oncological outcomes, China

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