破解维生素D与前列腺癌发病率和死亡率不一致关联的谜团：一项大规模嵌套病例对照研究
Disentangling discordant vitamin D associations with prostate cancer incidence and fatality in a large, nested case-control study
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影响因子:5.9
分区:医学2区 Top / 公共卫生1区
发表日期:2024 Aug 14
作者:
Lola Etiévant, Mitchell H Gail, Demetrius Albanes
DOI:
10.1093/ije/dyae110
摘要
在Alpha-Tocopherol, Beta-Carotene Cancer Prevention（ATBC）研究队列中发表的前列腺癌嵌套病例对照和生存分析提示，基线维生素D [25(OH)D]浓度较高的男性，既表现出（i）前列腺癌风险增加，也表现出（ii）前列腺癌特异性死亡率降低。为探究导致这种虚假关联的潜在因素，我们对ATBC研究中的病例对照数据进行了重新分析，评估了基线血清维生素D与前列腺癌风险及特异性死亡率的关系（包括1000名对照和1000名新发前列腺癌病例）。采用条件逻辑回归和Cox比例风险模型，分别估算前列腺癌风险的比值比和死亡风险的风险比，结合疾病严重程度进行分析。我们还用血清中α-生育酚（维生素E）、β-胡萝卜素和视黄醇（维生素A）的基线测定值重复了这些分析，并利用整个ATBC队列（n=29085）估算这些维生素与前列腺癌发生及死亡的边际关系。维生素D的分析结果与原始发表的结果高度一致，风险与死亡的关联相反。而α-生育酚、β-胡萝卜素和视黄醇的分析则显示这两者的关联一致。我们未发现嵌套病例对照数据存在伪影，也未观察到检测偏差或棘轮偏差，因此支持维生素D与前列腺癌特异性存活率呈有效的逆相关关系，值得在控制试验中进一步验证。
Abstract
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.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.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.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.Published by Oxford University Press on behalf of the International Epidemiological Association 2024.