Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
Int J Cancer. 2019 Apr 1;144(7):1522-1529. doi: 10.1002/ijc.31886. Epub 2018 Nov 13.
Use of vitamin K antagonists (VKAs) has been suggested to reduce the risk of prostate cancer. We conducted a nested case-control study using Danish demographic and health data registries and summarized existing evidence in a meta-analysis. The case-control study included all Danish men aged 40-85 years with incident histologically verified prostate adenocarcinoma between 2005 and 2015 (cases). For each case, we selected 10 age-matched controls. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CI) for prostate cancer associated with long-term VKA use adjusted for concomitant drug use, medical history and socioeconomic status. Among 38,832 prostate cancer cases, 1,089 (2.8%) had used VKAs for 3 or more years compared to 10,803 (2.8%) controls yielding a crude OR of 1.01 (95% CI, 0.95-1.08). Multivariable adjustment for covariates had limited influence on the association (OR, 1.03; 95% CI, 0.97-1.10). We observed no dose-response relationship (e.g. OR for 5-10 years of use, 1.06 95% CI, 0.97-1.16). We included 8 studies in the meta-analysis reporting effect estimates from 0.51 (95% CI, 0.23-1.13) to 1.10 (95% CI, 0.94-1.40). Using random effect methods, a pooled effect estimate of 0.86 (95% CI, 0.70-1.05) was obtained; however, there was considerable across-study heterogeneity (I : 93.9%). In conclusion, we did not observe a reduced risk of prostate cancer associated with VKA use in this nationwide study and, taken together with previous study findings, a major protective effect of VKAs against prostate cancer seems unlikely.
使用维生素 K 拮抗剂 (VKA) 已被证明可降低前列腺癌的风险。我们使用丹麦人口和健康数据登记处进行了一项嵌套病例对照研究，并对现有证据进行了荟萃分析。该病例对照研究纳入了 2005 年至 2015 年间所有 40-85 岁丹麦男性中经组织学证实的前列腺腺癌新发病例（病例）。对于每个病例，我们选择了 10 名年龄匹配的对照。我们使用条件逻辑回归估计了与长期 VKA 使用相关的前列腺癌的比值比 (OR)，95%置信区间 (CI) 调整了同时使用的药物、病史和社会经济状况。在 38832 例前列腺癌病例中，有 1089 例 (2.8%) 长期使用 VKA 超过 3 年，10803 例 (2.8%) 对照组的粗 OR 为 1.01 (95%CI，0.95-1.08)。调整协变量后的多变量调整对该相关性的影响有限 (OR，1.03；95%CI，0.97-1.10)。我们没有观察到剂量反应关系（例如，使用 5-10 年的 OR，1.06 95%CI，0.97-1.16）。我们纳入了 8 项研究进行荟萃分析，这些研究报告的效应估计值为 0.51（95%CI，0.23-1.13）至 1.10（95%CI，0.94-1.40）。使用随机效应方法，获得了 0.86（95%CI，0.70-1.05）的合并效应估计值；然而，研究间存在很大的异质性（I ：93.9%）。总之，在这项全国性研究中，我们没有观察到 VKA 使用与前列腺癌风险降低相关，并且结合以往的研究结果，VKA 对前列腺癌的主要保护作用似乎不太可能。
