Allopurinol and the incidence of bladder cancer

Abstract

Our aim is to investigate the risk association between allopurinol use and cancer incidence among gout patients using clinical evidence. Newly diagnosed male patients with gout, 20 years or older, were included after excluding those who had a diagnosis of type 2 diabetes, and were followed up for 12 years in a retrospective cohort study of one million outpatients of a national database. The gout patients were matched to male controls by age and first diagnosis date of gout disease. We then estimated the risk associations between incident cancers and duration of allopurinol use by Cox hazard regression, age-adjusted standardized incidence ratio, and incidence per 1000 person-years. A total of 24 050 gout patients and 76 129 controls were included. The incidence of all-cause cancers for gout patients and controls was 8.26 cases and 7.49 cases/1000 person-years, respectively; it was markedly increased in gout patients who used allopurinol for over 90 days. The hazard ratio of all-cause cancers was 1.21 (95% confidence interval=1.03-1.42, P=0.019) after adjustment for age and 2.26 for bladder cancer (95% confidence interval=1.32-3.87, P=0.003) on comparing those who used allopurinol for over 90 days with nonusers. Meanwhile, other cancers did not show the same significant result. We concluded that those who used allopurinol for a long duration had a higher occurrence of both bladder cancer and all-cause cancers in clinical evidence.

Hyperuricemia and gout are associated with cancer incidence and mortality: A meta‐analysis based on cohort studies

“…Therefore, we extracted these data one by one to analyze the pooled effect values of all tumors and single tumors. All included studies, except for one retrospective cohort study (Chen et al, ), were of prospective cohort designs. All subjects with a long‐term follow‐up were randomly selected from the general population or health surveys.…”

“…Multiple studies have found that hyperuricemia or gout was associated with higher cancer incidence and mortality (Boffetta, Nordenvall, Nyrén, & Ye, ; Chen, Hsieh, Liao, Chan, & Chang, ; Deng et al, ; Juraschek, Tunstall‐Pedoe, & Woodward, ; Kobylecki, Afzal, & Nordestgaard, ; Kolonel, Yoshizawa, Nomura, & Stemmermann, ; Kuo et al, ; Strasak et al, , ; Strasak et al, ; Taghizadeh, Vonk, & Boezen, ; Wandell, Carlsson, & Ljunggren, ; Yang et al, ; Yiu et al, ). However, at least two studies found no associations between cancer and hyperuricemia or gout (Hiatt & Fireman, ; Wu et al, ), and even one study suggested that the lower SUA levels may lead to a higher incidence of lung cancer (Horsfall, Nazareth, & Petersen, ).…”

Xanthine dehydrogenase downregulation promotes TGFβ signaling and cancer stem cell-related gene expression in hepatocellular carcinoma

“… 8 In support of this hypothesis, a recent retrospective cohort study found that use of allopurinol, an XDH/XOR inhibitor, for >3 months may significantly increase the incidence of both bladder cancer and all other cancers. 48 Moreover, XDH inhibition by allopurinol may help cancer cells to escape immune surveillance. 49 Although recent publications indicated that advanced cancer patients will benefit from XDH inhibition, 50 , 51 long-term follow-up of patients receiving XDH inhibitors treatment may be necessary to prevent detrimental outcomes.…”

Epidemiology and health-related services

“…Specifically bladder cancer has been shown to be associated with long-term allopurinol use [63]. Erectile dysfunction has also been reported to be more common in patients with gout [64], whereas its relationship with ULT, and specifically to xanthine-oxidase inhibitors, has not been yet studied.…”