Association Between Urothelial Carcinoma After Kidney Transplantation and Aristolochic Acid Exposure: The Potential Role of Aristolochic Acid in HRas and TP53 Gene Mutations

Abstract

Objective We sought to investigate the association between urothelial carcinoma (UC) after kidney transplantation and aristolochic acid (AA) exposure, and to explore the potential role of AA in HRas and TP53 gene mutations. Materials and Methods UC was confirmed in 100 of 3790 patients who underwent kidney transplantation between January 1974 and May 2011. We retrospectively analyzed clinical data for these patients. Malignancies were identified in 136 patients (15 males and 85 females, of age range 27–71 years mean, 53.2 ± 6.3). UC was the most common diagnosis (100/136; 73.5%). The median time from transplantation to the first confirmed diagnosis of a tumor was 34.5 months (range, 2–273). Polymerase chain reaction–based resequencing methods were used to detect mutations in the target regions of exons 2 and 3 of the HRas gene and exons 5, 6, 7, and 8 of the TP53 gene in 90 of 100 samples. Results UC was identified in 53 of 380 patients exposed to AA and 47 of 3410 patients not exposed to AA ( P < 0.05). Pathologic examination of the UC specimens from AA-exposed patients identified heterozygous HRas changes in 3 cases, and deletion or replacement mutations in the TP53 gene in 4. No genetic mutations were observed among the control group. Conclusion UC after kidney transplantation significantly correlated with AA exposure; however, there seemed to be no significant difference in mutations in exons 2 and 3 of the HRas gene and those in exons 5, 6, 7, and 8 of the TP53 gene in terms of tumor development, a result that is inconsistent with previous studies.