BACKGROUND Published analyses of prostate cancer nested case-control and survival data in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort suggested that men with higher baseline vitamin D [25(OH)D] concentrations have both (i) increased prostate cancer risk and (ii) decreased prostate cancer-specific fatality. METHODS To investigate possible factors responsible for a spurious association with prostate cancer fatality, we reanalysed baseline serum vitamin D associations with prostate cancer risk and prostate cancer-specific fatality in case-control data nested within the ATBC Study (1000 controls and 1000 incident prostate cancer cases). Conditional logistic regression and Cox proportion hazard models were used, respectively, to estimate odds ratios for risk and hazard ratios for prostate cancer-specific fatality, overall and by disease aggressiveness. We replicated these case-control analyses using baseline serum measurements of alpha-tocopherol (vitamin E), beta-carotene and retinol (vitamin A), and used the entire ATBC Study cohort (n = 29 085) to estimate marginal associations between these baseline vitamins and prostate cancer incidence and fatality following blood collection. RESULTS Vitamin D analyses agreed closely with those originally published, with opposite risk and fatality associations. By contrast, the analyses of alpha-tocopherol, beta-carotene and retinol yielded concordant associations for prostate cancer incidence and prostate cancer-specific fatality. CONCLUSIONS We found evidence of neither artefacts in the nested prostate cancer case-control data set nor detection or collider biases in the fatality analyses. The present findings therefore support a valid inverse (i.e. beneficial) association between vitamin D and prostate cancer-specific survival that warrants further evaluation, including possibly in controlled trials.

中文翻译：

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在一项大型巢式病例对照研究中，阐明了维生素 D 与前列腺癌发病率和死亡率之间不一致的关联。


背景 已发表的α-生育酚、β-胡萝卜素癌症预防 (ATBC) 研究队列中前列腺癌巢式病例对照和生存数据的分析表明，基线维生素 D [25(OH)D] 浓度较高的男性具有以下两种情况：增加前列腺癌风险，并且 (ii) 降低前列腺癌特异性死亡率。方法 为了调查与前列腺癌死亡率虚假关联的可能因素，我们重新分析了 ATBC 研究中病例对照数据（1000 名对照者和 1000 名前列腺癌发病者）中基线血清维生素 D 与前列腺癌风险和前列腺癌特异性死亡率的关联。例）。分别使用条件逻辑回归和 Cox 比例风险模型来估计前列腺癌特异性死亡率的总体风险比和疾病侵袭性的风险比。我们使用 α-生育酚（维生素 E）、β-胡萝卜素和视黄醇（维生素 A）的基线血清测量值重复了这些病例对照分析，并使用整个 ATBC 研究队列（n = 29 085）来估计这些基线之间的边际关联采血后维生素与前列腺癌的发病率和死亡率。结果维生素 D 分析与最初发表的分析结果非常一致，但风险和死亡率相关性相反。相比之下，对α-生育酚、β-胡萝卜素和视黄醇的分析得出了前列腺癌发病率和前列腺癌特异性死亡率之间的一致关联。结论 我们既没有在嵌套前列腺癌病例对照数据集中发现人为因素，也没有在死亡率分析中发现检测或碰撞偏差的证据。因此，目前的发现支持有效的逆（即 维生素 D 与前列腺癌特异性生存之间的有益）关联值得进一步评估，包括可能在对照试验中进行评估。