University of Tampere, Faculty of Medicine and Life Sciences, Tampere, Finland.
Tampere University Hospital, Department of Urology, Tampere, Finland.
Prostate Cancer Prostatic Dis. 2019 Sep;22(3):483-490. doi: 10.1038/s41391-019-0129-2. Epub 2019 Jan 29.
Allopurinol reduces oxidative stress and may thus have an anti-inflammatory effect. Previous studies suggest that allopurinol use might decrease the risk of prostate cancer (PCa) among gout patients. We studied the association between allopurinol use and PCa incidence.
The cohort consists of 76,874 men without prevalent PCa, originally identified for the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). The follow-up started at entry to the trial. We excluded men using allopurinol in the year before entry (wash-out). PCa cases detected during 1996-2015 were identified from the Finnish Cancer Registry. Information on tumor Gleason score and TNM stage were obtained from medical files. Information on PSA level was obtained from screening samples for men in the FinRSPC screening arm and from laboratory databases for men in the control arm. Information on BMI was based on a questionnaire sent to men in the FinRSPC screening arm in 2004-2008. Drug purchase information were obtained from the national prescription database. We used Cox regression (adjusted for age, FinRSPC trial arm, PCa family history and use of other medication) to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of PCa risk by allopurinol use. We analyzed medication as a time-dependent variable to minimize immortal time bias.
There were 9062 new PCa diagnoses in the cohort. Follow-up time did not differ by allopurinol use (median 17 yr; IQR 11-19 vs median 17 yr; IQR 12.33-19). The risk of PCa did not differ by allopurinol use (multivariable adjusted HR 1.03; 95% CI 0.92-1.16). Allopurinol use did not associate with the risk of high-grade or metastatic cancer. Cumulative duration or average yearly dose of allopurinol use showed no association with PCa risk. No delayed risk associations were observed in the lag-time analyses.
We observed no difference in the PCa risk by allopurinol use.
别嘌醇可降低氧化应激，从而具有抗炎作用。先前的研究表明，别嘌醇的使用可能会降低痛风患者患前列腺癌（PCa）的风险。我们研究了别嘌醇的使用与 PCa 发病率之间的关系。
该队列包括 76874 名无前列腺癌既往史的男性，最初是为芬兰前列腺癌筛查随机研究（FinRSPC）确定的。随访从进入试验开始。我们排除了在进入前一年（洗脱期）使用别嘌醇的男性。1996-2015 年间检测到的 PCa 病例是从芬兰癌症登记处获得的。肿瘤 Gleason 评分和 TNM 分期的信息是从医疗档案中获得的。PSA 水平的信息是从 FinRSPC 筛查组的筛查样本和对照组的实验室数据库中获得的。BMI 的信息基于 2004-2008 年发给 FinRSPC 筛查组男性的问卷。药物购买信息是从国家处方数据库中获得的。我们使用 Cox 回归（按年龄、FinRSPC 试验臂、PCa 家族史和其他药物使用情况进行调整）来计算别嘌醇使用与 PCa 风险的风险比（HR）和 95%置信区间（CI）。我们将药物作为时间依赖性变量进行分析，以最大程度地减少不朽时间偏差。
队列中有 9062 例新的 PCa 诊断。随访时间不因别嘌醇的使用而不同（中位数 17 年；IQR 11-19 与中位数 17 年；IQR 12.33-19）。别嘌醇的使用与 PCa 风险无差异（多变量调整 HR 1.03；95%CI 0.92-1.16）。别嘌醇的使用与高级别或转移性癌症的风险无关。别嘌醇使用的累积持续时间或平均每年剂量与 PCa 风险无关。在滞后时间分析中未观察到延迟的风险关联。
我们观察到别嘌醇的使用与 PCa 风险之间没有差异。
