BACKGROUND: Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors. METHODS: The incidence of ureteral cancer was estimated from the Cancer Incidence in Five Continents Plus and Global Cancer Observatory databases. We analyzed the (1) global incidence of ureteral cancer by region, country, sex, and age group by age-standardized rates (ASR); (2) associated risk factors on a population level by univariable linear regression with logarithm transformation; and (3) incidence trend of ureteral cancer by sex and age group in different countries by Average Annual Percentage Change (AAPC). RESULTS: The global age-standardized rate of ureteral cancer incidence in 2022 was 22.3 per 10,000,000 people. Regions with higher human development index (HDI), such as Europe, Northern America, and East Asia, were found to have a higher incidence of ureteral cancer. Higher HDI and gross domestic product (GDP) and a higher prevalence of smoking, alcohol drinking, physical inactivity, unhealthy dietary, obesity, hypertension, diabetes, and lipid disorder were associated with higher incidence of ureteral cancer. An overall increasing trend of ureteral cancer incidence was observed for the past decade, especially among the female population. CONCLUSIONS: Although ureteral cancer was relatively rare, the number of cases reported was rising over the world. The rising trends among females were more evident compared with the other subgroups, especially in European countries. Further studies could be conducted to examine the reasons behind these epidemiological changes and confirm the relationship with the risk factors identified.

• Klíčová slova
• Incidence, Risk factors, Temporal trends, Ureteral cancer,
• MeSH
• celosvětové zdraví MeSH
• dospělí MeSH
• globální zátěž nemocemi trendy   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory močovodu * epidemiologie   MeSH
• registrace * MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Aristolochic acids (AAs) are a group of naturally occurring compounds present in many plant species of the Aristolochiaceae family. Exposure to AA is a significant risk factor for severe nephropathy, and urological and hepatobiliary cancers (among others) that are often recurrent and characterized by the prominent mutational fingerprint of AA. However, herbal medicinal products that contain AA continue to be manufactured and marketed worldwide with inadequate regulation, and possible environmental exposure routes receive little attention. As the trade of food and dietary supplements becomes increasingly globalized, we propose that further inaction on curtailing AA exposure will have far-reaching negative effects on the disease trends of AA-associated cancers. Our Review aims to systematically present the historical and current evidence for the mutagenicity and carcinogenicity of AA, and the effect of removing sources of AA exposure on cancer incidence trends. We discuss the persisting challenges of assessing the scale of AA-related carcinogenicity, and the obstacles that must be overcome in curbing AA exposure and preventing associated cancers. Overall, this Review aims to strengthen the case for the implementation of prevention measures against AA's multifaceted, detrimental and potentially fully preventable effects on human cancer development.

• MeSH
• kyseliny aristolochové * toxicita   MeSH
• lidé MeSH
• mutageneze MeSH
• nádory * chemicky indukované   epidemiologie   MeSH
• veřejné zdravotnictví MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• aristolochic acid I MeSH Prohlížeč
• kyseliny aristolochové * MeSH

Aristolochic acid (AA) is a plant alkaloid that causes aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN), unique renal diseases frequently associated with upper urothelial cancer (UUC). This review summarizes the significance of AA-derived DNA adducts in the aetiology of UUC leading to specific A:T to T:A transversion mutations (mutational signature) in AAN/BEN-associated tumours, which are otherwise rare in individuals with UCC not exposed to AA. Therefore, such DNA damage produced by AA-DNA adducts is one rare example of the direct association of exposure and cancer development (UUC) in humans, confirming that the covalent binding of carcinogens to DNA is causally related to tumourigenesis. Although aristolochic acid I (AAI), the major component of the natural plant extract AA, might directly cause interstitial nephropathy, enzymatic activation of AAI to reactive intermediates capable of binding to DNA is a necessary step leading to the formation of AA-DNA adducts and subsequently AA-induced malignant transformation. Therefore, AA-DNA adducts can not only be utilized as biomarkers for the assessment of AA exposure and markers of AA-induced UUC, but also be used for the mechanistic evaluation of its enzymatic activation and detoxification. Differences in AA metabolism might be one of the reasons for an individual's susceptibility in the multi-step process of AA carcinogenesis and studying associations between activities and/or polymorphisms of the enzymes metabolising AA is an important determinant to identify individuals having a high risk of developing AA-mediated UUC.

• Klíčová slova
• DNA adduct formation, aristolochic acid, carcinogenicity, mutagenesis, nephrotoxicity,
• MeSH
• adukty DNA metabolismus   MeSH
• balkánská nefropatie etiologie   metabolismus   MeSH
• biologické markery * MeSH
• karcinogeny chemie   metabolismus   MeSH
• kyseliny aristolochové chemie   metabolismus   MeSH
• lidé MeSH
• náchylnost k nemoci MeSH
• nádorová transformace buněk genetika   metabolismus   MeSH
• urologické nádory etiologie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• adukty DNA MeSH
• biologické markery * MeSH
• karcinogeny MeSH
• kyseliny aristolochové MeSH

Balkan endemic nephropathy (BEN) is a unique, chronic renal disease frequently associated with upper urothelial cancer (UUC). It only affects residents of specific farming villages located along tributaries of the Danube River in Bosnia-Herzegovina, Croatia, Macedonia, Serbia, Bulgaria, and Romania where it is estimated that ~100,000 individuals are at risk of BEN, while ~25,000 have the disease. This review summarises current findings on the aetiology of BEN. Over the last 50 years, several hypotheses on the cause of BEN have been formulated, including mycotoxins, heavy metals, viruses, and trace-element insufficiencies. However, recent molecular epidemiological studies provide a strong case that chronic dietary exposure to aristolochic acid (AA) a principal component of Aristolochia clematitis which grows as a weed in the wheat fields of the endemic regions is the cause of BEN and associated UUC. One of the still enigmatic features of BEN that need to be resolved is why the prevalence of BEN is only 3-7 %. This suggests that individual genetic susceptibilities to AA exist in humans. In fact dietary ingestion of AA along with individual genetic susceptibility provides a scenario that plausibly can explain all the peculiarities of BEN such as geographical distribution and high risk of urothelial cancer. For the countries harbouring BEN implementing public health measures to avoid AA exposure is of the utmost importance because this seems to be the best way to eradicate this once mysterious disease to which the residents of BEN villages have been completely and utterly at mercy for so long.

• Klíčová slova
• Aristolochic acid, Aristolochic acid nephropathy, Balkan endemic nephropathy, Disease aetiology, Environmental and genetic factors, Upper urothelial cancer,
• MeSH
• Aristolochia chemie   růst a vývoj   toxicita   MeSH
• balkánská nefropatie chemicky indukované   epidemiologie   patofyziologie   prevence a kontrola   MeSH
• dieta škodlivé účinky   MeSH
• endemické nemoci * MeSH
• faktory vyvracející (epidemiologie) MeSH
• karcinogeny životního prostředí analýza   toxicita   MeSH
• kontaminace potravin * prevence a kontrola   MeSH
• kyseliny aristolochové analýza   toxicita   MeSH
• ledviny účinky léků   patofyziologie   MeSH
• léková rezistence MeSH
• lidé MeSH
• medicína založená na důkazech * MeSH
• mouka škodlivé účinky   analýza   MeSH
• plevel chemie   růst a vývoj   toxicita   MeSH
• prevalence MeSH
• pšenice růst a vývoj   MeSH
• riziko MeSH
• semena rostlinná růst a vývoj   MeSH
• urologické nádory chemicky indukované   epidemiologie   patofyziologie   prevence a kontrola   MeSH
• zemědělské plodiny růst a vývoj   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• východní Evropa epidemiologie   MeSH
• Názvy látek
• aristolochic acid I MeSH Prohlížeč
• karcinogeny životního prostředí MeSH
• kyseliny aristolochové MeSH