Allopurinol and risk of benign prostatic hyperplasia in a Finnish population-based cohort

Kukko, Ville; Kaipia, Antti; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo L.J.; Auvinen, Anssi; Murtola, Teemu J.

doi:10.1038/s41391-017-0031-8

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…Previous clinical trials have shown that allopurinol has a positive association with prostate cancers, patients treated with allopurinol could decreased the incidence of prostate cancer. And the combined use of allopurinol for one month can reduce the level of NF kappaB in patients with colonic adenoma [16][17][18][19]. It is suggested that the drug that reduces uric acid levels have potential anticancer efects and provides a new idea for tumor treatment.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of PDZK1 in Hepatocellular Carcinoma Complicated with Hyperuricemia

Guo

Jiang

Quan

et al. 2022

Journal of Oncology

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Background. Hepatocellular carcinoma (HCC) is a kind of primary liver cancer that accounts for more than 90% of primary hepatocellular carcinomas. Hyperuricemia is closely related to the development, recurrence, metastasis, and prognosis of cancer. Previous studies have proved that the serum uric acid level can increase the incidence rate and mortality of malignant tumors. However, the specific pathogenesis remains unstudied. Methods. RT-qPCR analysis showed that the mRNA expression of PDZK1 and ABCG2 increased significantly after HCC cells were exposed to different concentrations of soluble uric acid (2.5, 5, 10, 20 mg/dl) for 24 hours. Then, in HCC shRNAs, PDZK1, or over expression PDZK1 were used. CCK8, wound healing, and Transwell assay showed that PDZK1 regulates cell proliferation, invasion, and migration. Flow cytometry results revealed that PDZK1 affects cell apoptosis. Western blot results show that PDZK1 affects the STAT3/C-myc pathway. Then, in vivo tumorigenesis, allopurinol maybe an effective drug to advance: the prognosis of HCC. Results. In our study, RT-qPCR analysis showed that the mRNA expression of PDZK1 and ABCG2 increased significantly after different concentrations of soluble uric acid in HCC. Then, PDZK1 affects the proliferation, migration, and apoptosis of HCC through the STAT3/C-myc pathway. Conclusions. Hyperuricemia response affects the expression of PDZK1; PDZK1 affects the proliferation, migration, and apoptosis through the STAT3/C-myc pathway in hepatocellular carcinoma. It is suggested that PDZK1 maybe closely related to the occurrence, development, and prognosis of HCC and allopurinol maybe have potential anticancer effects.

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Section: Introductionmentioning

confidence: 99%

Mechanism of PDZK1 in Hepatocellular Carcinoma Complicated with Hyperuricemia

Guo

Jiang

Quan

et al. 2022

Journal of Oncology

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“…Our population-based cohort study did not support these findings. Although allopurinol use was associated with a lower incidence of benign prostatic hyperplasia, we did not find any differences in prostate cancer incidence [ 19 , 20 ]. Most studies evaluating possible association between allopurinol (or gout) and PCa are based on Taiwanese registries.…”

Section: Introductionmentioning

confidence: 77%

Allopurinol and prostate cancer survival in a Finnish population-based cohort

Kukko

Kaipia

Talala

et al. 2022

Prostate Cancer Prostatic Dis

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Background Allopurinol is gout medication that inhibits uric acid formation. Its possible anti-carcinogenic properties have been under research in past years. Studies based on Taiwanese registries showed that long term allopurinol use might reduce prostate cancer (PCa) incidence. However, our studies based on Finnish registries did not support those findings. In this study, we evaluate whether allopurinol use is associated with prostate cancer-specific survival (CSS) or overall survival (OS) in a Finnish population-based cohort. Methods The study cohort was originally enrolled for the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). We included all newly diagnosed PCa cases during 1996–2015, 9252 men in total. Information on allopurinol purchases was from the national prescription registry of the Social Insurance Institution of Finland. Information about deaths, treatments, and use of other medications was obtained from registries, and tumor stage and PSA at diagnosis from medical records. Follow-up started at diagnosis, and we analysed separately two endpoints: PCa-specific death and overall death. We used an extended Cox regression with adjustment for age at diagnosis, Charlson comorbidity index, FinRSPC trial arm, use of other drugs and EAU PCa risk group. Results During a median follow-up of 9.86 years, 2942 deaths occurred, including 883 from PCa. There was no difference in CSS between allopurinol user and non-users, but allopurinol users had lower OS (multivariable-adjusted hazard ratio 1.77; 95% CI: 1.57–2.00). However, this decrease in OS was mitigated along with increasing intensity of allopurinol use. Conclusions We found no marked difference in CSS by allopurinol use. Allopurinol users had lower OS but there were no significant differences by duration or intensity of allopurinol use. Allopurinol use may not have anticancer effects against prostate cancer; instead, it may be a surrogate for metabolic problems causing shorter OS among men with PCa.

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“…Previous studies mainly investigated prostate pathology related to hyperuricemia or gout. Men undergoing ULT had a lower risk of BPH than those without ULT [ 14 ]. This result is potentially explained by oxidative stress associated with hyperuricemia and the antioxidant effects of ULT.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress was considered to promote benign prostate hyperplasia (BPH) through activation of the inflammasome in response to UA [ 13 ]. Meanwhile, one population-based study demonstrated that uric acid lowering treatment (ULT) was associated with lower use of BPH medications and less frequent diagnosis of LUTS than in those who were not treated with ULT [ 14 ]. Another group found that ULT reduced prostate cancer cell growth by 37% [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Higher Levels of Serum Uric Acid Have a Significant Association with Lower Incidence of Lower Urinary Tract Symptoms in Healthy Korean Men

2022

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Gout has been correlated with the risk of incident benign prostatic hyperplasia. In line with increasing prevalence of hyperuricemia, the aim of this study was to investigate the relationship between serum uric acid (SUA) level and the incidence of lower urinary tract symptoms (LUTS) among clinically healthy middle-aged men. We performed a cohort study in 101,091 Korean men without LUTS at baseline who completed health checkups between 2011 and 2016. LUTS were evaluated using the International Prostate Symptom Score, where a score ≥ 8 was defined as significant LUTS. Men were divided into six groups according to their SUA levels in mg/dL (<5.5, 5.5–6.4, 6.5–7.4, 7.5–8.4, 8.5–9.4, and ≥9.5). Throughout the follow-up—encompassing a total of 358,982.6 person years—13,424 people had significant LUTS (37.3 per 1000 person years for incidence rate). The multivariable models demonstrated that the highest level of SUA (≥9.5 mg/dL) was related to the lowest risk of significant LUTS compared with the reference category (<5.5 mg/dL) (0.77 (95% CI 0.59–0.99) for adjusted HR). In this large cohort composed of middle-aged men, higher SUA levels were related to a reduced risk of LUTS. This result suggests another potential role of SUA in restraining LUTS. Additional studies are needed to explain the underlying biological mechanisms of this phenomenological relationship.

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Allopurinol and risk of benign prostatic hyperplasia in a Finnish population-based cohort

Abstract: We found that allopurinol use is associated with lowered risk of BPH medication, diagnosis and surgery. A possible explanation could be antioxidative effects of urate-lowering allopurinol.

Cited by 7 publications

References 21 publications

Mechanism of PDZK1 in Hepatocellular Carcinoma Complicated with Hyperuricemia

Mechanism of PDZK1 in Hepatocellular Carcinoma Complicated with Hyperuricemia

Allopurinol and prostate cancer survival in a Finnish population-based cohort

Higher Levels of Serum Uric Acid Have a Significant Association with Lower Incidence of Lower Urinary Tract Symptoms in Healthy Korean Men

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