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芬兰人群队列中别嘌醇与前列腺癌生存率

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

作者信息

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

机构信息

Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

Department of Urology, Tampere University Hospital, Tampere, Finland.

出版信息

Prostate Cancer Prostatic Dis. 2024 Mar;27(1):73-80. doi: 10.1038/s41391-022-00597-4. Epub 2022 Sep 21.

Abstract

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.

摘要

背景

别嘌醇是一种抑制尿酸形成的痛风药物。其可能的抗癌特性在过去几年中一直在研究。基于台湾登记处的研究表明,长期使用别嘌醇可能会降低前列腺癌(PCa)的发病率。然而,我们基于芬兰登记处的研究并不支持这些发现。在本研究中,我们评估在芬兰基于人群的队列中,使用别嘌醇是否与前列腺癌特异性生存(CSS)或总生存(OS)相关。

方法

研究队列最初纳入芬兰前列腺癌筛查随机研究(FinRSPC)。我们纳入了1996年至2015年期间所有新诊断的PCa病例,共9252名男性。别嘌醇购买信息来自芬兰社会保险机构的国家处方登记处。死亡、治疗和其他药物使用信息从登记处获得,诊断时的肿瘤分期和前列腺特异性抗原(PSA)从病历中获取。随访从诊断开始,我们分别分析了两个终点:PCa特异性死亡和全因死亡。我们使用扩展的Cox回归,并对诊断时的年龄、Charlson合并症指数、FinRSPC试验组、其他药物使用情况和欧洲泌尿外科协会(EAU)PCa风险组进行了调整。

结果

在中位随访9.86年期间,发生了2942例死亡,其中883例死于PCa。别嘌醇使用者和非使用者之间的CSS没有差异,但别嘌醇使用者的OS较低(多变量调整风险比1.77;95%置信区间:1.57 - 2.00)。然而,随着别嘌醇使用强度的增加,OS的这种降低有所缓解。

结论

我们发现使用别嘌醇在CSS方面没有显著差异。别嘌醇使用者的OS较低,但别嘌醇使用的持续时间或强度没有显著差异。使用别嘌醇可能对前列腺癌没有抗癌作用;相反,它可能是导致PCa男性OS较短的代谢问题的一个替代指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/649c/10876474/c829ef97f296/41391_2022_597_Fig1_HTML.jpg

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