Parker Jonathan, Crawley Danielle, Garmo Hans, Lindahl Bertil, Styrke Johan, Adolfsson Jan, Lambe Mats, Stattin Pär, Van Hemelrijck Mieke, Beckmann Kerri
Translational Oncology and Urology Research Group, School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.
Regional Cancer Centre Uppsala Orebro, Uppsala, Sweden.
Front Oncol. 2020 Oct 8;10:571838. doi: 10.3389/fonc.2020.571838. eCollection 2020.
Existing literature examining warfarin's association with prostate cancer (PCa) risk provides conflicting results, while the association with direct oral anticoagulants (DOACs) has not yet been studied. We investigated the association of warfarin and DOAC use on PCa risk among men within the population-based Prostate Cancer database Sweden (PCBaSe), using a case-control design. The study population included PCa cases diagnosed 2014-2016 and five age-matched PCa-free controls. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for PCa associated with warfarin and DOAC use, adjusted for marital status, education level, other drug use, and comorbidities. Among 31,591 cases and 156,802 controls, there were 18,522 (9.8%) warfarin and 4,455 (2.4%) DOAC users. Warfarin ever-use was associated with reduced risk of PCa overall (OR 0.92 95% CI 0.88-0.96) as were both past and current use. DOAC use was not associated with PCa risk. For some warfarin exposures, decreased risk was observed for unfavorable PCa (high risk/locally advanced/distant metastatic) but not with favorable PCa (low/intermediate risk). Increased risk of favorable PCa was observed for men whose initial warfarin exposure occurred in the 12 month period before diagnosis (OR 1.39; 95% CI 1.13-1.70). Our findings are consistent with previous publications reporting decreased PCa risk with warfarin exposure. Increased risk of favorable PCa suggests detection bias due to increased prostate specific antigen testing when starting on warfarin. Decreased overall PCa risk could reflect bias due to reduced biopsy rates among long-term warfarin users.
现有研究华法林与前列腺癌(PCa)风险相关性的文献结果相互矛盾,而华法林与直接口服抗凝剂(DOACs)的相关性尚未得到研究。我们采用病例对照设计,在基于人群的瑞典前列腺癌数据库(PCBaSe)中调查了华法林和DOACs的使用与男性PCa风险之间的相关性。研究人群包括2014年至2016年诊断出的PCa病例以及五名年龄匹配的无PCa对照者。使用条件逻辑回归来估计与华法林和DOACs使用相关的PCa的比值比(OR)及95%置信区间(CI),并对婚姻状况、教育水平、其他药物使用情况和合并症进行了调整。在31,591例病例和156,802名对照者中,有18,522名(9.8%)华法林使用者和4,455名(2.4%)DOACs使用者。华法林的既往使用与总体PCa风险降低相关(OR 0.92,95% CI 0.88 - 0.96),既往使用和当前使用均如此。DOACs的使用与PCa风险无关。对于某些华法林暴露情况,观察到不良PCa(高风险/局部晚期/远处转移)的风险降低,但有利PCa(低/中度风险)则不然。对于在诊断前12个月内首次暴露于华法林的男性,观察到有利PCa的风险增加(OR 1.39;95% CI 1.13 - 1.70)。我们的研究结果与先前报道华法林暴露会降低PCa风险的文献一致。有利PCa风险增加表明,开始使用华法林时由于前列腺特异性抗原检测增加而导致检测偏倚。总体PCa风险降低可能反映了长期华法林使用者活检率降低所致的偏倚。