A systematic review of the possible carcinogenic role of the aristolochic acid

Aristolochic acid (AA) is a bioactive component of Chinese herbs, dietary supplements, slimming pills and contaminated flour, which is known to induce chronic tubulointerstitial disease. AA is also shown to be involved in the genesis of the upper urinary tract urothelial carcinoma (UTUC) and some other cancers, but its tumorigenic role is far to be understood. We performed a systematic literature review regarding the involvement of AA in malignant processes and molecular pathways of carcinogenesis. Twenty representative papers were selected for this review. These papers reveal that AA exposure increases the risk for UTUC, renal cell carcinoma, hepatocellular carcinoma, gastric and small intestine cancer. The role of AA in lymphomagenesis is also proposed. The A:T to T:A transversions occurring in the 5'-CpApG-3' trinucleotide context of the TP53 gene is considered to be the signature mutation of AA. Genes including H-ras, FGFR3, N-ras and BRCA2 are also involved. For further understanding of AA's role in tumorigenesis, the exploration of the AA's molecular signature is necessary.