Aristolochic Acid in the Etiology of Renal Cell Carcinoma
Menée à Taïwan à partir de données portant sur 5 709 patients atteints d'un carcinome à cellules rénales et sur 22 836 témoins, cette étude évalue l'association entre une exposition à l'acide aristolochique présent dans certaines plantes utilisées en médecine traditionnelle chinoise et le risque de développer la maladie
Background: Aristolochia species used in the practice of traditional herbal medicine contains aristolochic acid (AA), an established human carcinogen contributing to urothelial carcinomas of the upper urinary tract. AA binds covalently to genomic DNA, forming aristolactam (AL)–DNA adducts. Here we investigated whether AA is also an etiologic factor in clear cell renal cell carcinoma (ccRCC). Methods: We conducted a population-based case–control study to investigate the linkage between Aristolochia prescription history, cumulative AA consumption, and ccRCC incidence in Taiwan (5,709 cases and 22,836 matched controls). The presence and level of mutagenic dA-AL-I adducts were determined in the kidney DNA of 51 Taiwanese ccRCC patients. The whole-exome sequences of ccRCC tumors from 10 Taiwanese ccRCC patients with prior exposure to AA were determine Results: Cumulative ingestion of more than 250 mg of AA increased risk of ccRCC (OR, 1.25), and we detected dA-AL-I adducts in 76% of Taiwanese ccRCC patients. Furthermore, the distinctive AA mutational signature was evident in six of 10 sequenced ccRCC exomes from Taiwanese patients. Conclusions: This study strongly suggests that AA contributes to the etiology of certain RCCs Impact: The current study offers compelling evidence implicating AA in a significant fraction of the RCC arising in Taiwan and illustrates the power of integrating epidemiologic, molecular, and genetic data in the investigation of cancer etiology. Cancer Epidemiol Biomarkers Prev; 25(12); 1–9. ©2016 AACR.%U http://cebp.aacrjournals.org/content/cebp/early/2016/11/18/1055-9965.EPI-16-0219.full.pdf