Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases: A Systematic Review and Meta-analysis.
Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases: A Systematic Review and Meta-analysis.
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DOI：
10.1001/jamanetworkopen.2020.25515
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发表时间：
2020-11-02
影响因子：
13.8
通讯作者：
Kobayashi LC
中科院分区：
文献类型：
--
作者：
Ospina-Romero M;Glymour MM;Hayes-Larson E;Mayeda ER;Graff RE;Brenowitz WD;Ackley SF;Witte JS;Kobayashi LC
癌症和随后的阿尔茨海默病（AD）之间是否存在关联，这种发现与方法学偏倚而不是真正的共同病因学相关的可能性有多大？在这项对22项队列和病例对照研究（代表9 630 435名个体）进行的系统性综述和荟萃分析中，癌症诊断与AD发病率降低11%相关。偏倚调整后的元回归分析表明，竞争风险和诊断偏倚不太可能解释所观察到的相关性，而生存偏倚仍有待排除。观察到的癌症和AD之间的负相关似乎不是竞争风险、已知混杂或诊断偏倚的结果。观察性研究一致报告癌症和阿尔茨海默病（AD）之间的负相关。共享的逆病因学机制可能解释这一现象，但在现有的研究中的方法学偏差的系统评价是必要的。系统地审查和荟萃分析癌症与随后AD之间相关性的证据，系统地识别研究中潜在的方法学偏倚，并估计这些偏倚对癌症与AD之间估计汇总相关性的影响。截至2020年9月2日，所有语言出版物均来自PubMed、Embase和PsycINFO数据库。纵向队列研究和病例对照研究，研究有任何癌症类型、前列腺癌、乳腺癌、结直肠癌或非黑色素瘤皮肤癌病史的老年人相对于无癌症病史的老年人患AD的风险。两名评价者独立地提取数据，并评估与混杂因素、诊断偏倚、竞争风险或生存偏倚相关的研究偏倚。随机效应荟萃分析用于提供癌症和AD之间关联的汇总估计值。使用元回归评估观察到的合并估计值是否可归因于每种偏倚。本研究根据系统性综述和荟萃分析首选报告项目（PRISMA）报告指南设计和实施。AD的发病率、风险或优势比，比较既往有癌症诊断的老年人与无癌症诊断的老年人。总共确定了19项队列研究和3项病例对照研究，涉及任何癌症类型（n = 13）、前列腺癌（n = 5）、乳腺癌（n = 1）和非黑色素瘤皮肤癌（n = 3）与AD之间的关联，代表9 630 435例个体。在所有研究中，癌症与AD发病率降低相关（队列研究：随机效应风险比，0.89; 95%CI，0.79-1.00;病例对照研究：随机效应比值比，0.75; 95%CI，0.61-0.93）。混杂因素控制不足或不适当或AD诊断偏倚可能性较大的研究的平均风险比更接近零值，表明这些偏倚无法解释观察到的负相关。竞争风险偏倚是罕见的。生存偏倚可能性较大的研究的平均风险比远离零值。癌症和AD之间的弱负相关可能反映了共同的逆病因机制或生存偏倚，但不太可能归因于诊断偏倚、竞争风险偏倚或对潜在混杂因素的控制不足或不当。这项系统性综述和荟萃分析评估了队列研究和病例对照研究中的方法学偏倚（而非常见病因）解释老年人癌症与随后的阿尔茨海默病发病率之间负相关的可能性。
Does an association exist between cancer and subsequent Alzheimer disease (AD), and how likely is it that such a finding is associated with methodological bias rather than with a true common etiology? In this systematic review and meta-analysis of 22 cohort and case-control studies representing 9 630 435 individuals, cancer diagnosis was associated with 11% decreased incidence of AD. Bias-adjusted metaregressions suggested that competing risks and diagnostic bias were unlikely explanations for the observed association, whereas survival bias remains to be ruled out. The observed inverse association between cancer and AD does not seem to be a consequence of competing risks, known confounding, or diagnostic bias. Observational studies consistently report inverse associations between cancer and Alzheimer disease (AD). Shared inverse etiological mechanisms might explain this phenomenon, but a systematic evaluation of methodological biases in existing studies is needed. To systematically review and meta-analyze evidence on the association between cancer and subsequent AD, systematically identify potential methodological biases in studies, and estimate the influence of these biases on the estimated pooled association between cancer and AD. All-language publications were identified from PubMed, Embase, and PsycINFO databases through September 2, 2020. Longitudinal cohort studies and case-control studies on the risk of AD in older adults with a history of any cancer type, prostate cancer, breast cancer, colorectal cancer, or nonmelanoma skin cancer, relative to those with no cancer history. Two reviewers independently abstracted the data and evaluated study biases related to confounding, diagnostic bias, competing risks, or survival bias. Random-effects meta-analysis was used to provide pooled estimates of the association between cancer and AD. Metaregressions were used to evaluate whether the observed pooled estimate could be attributable to each bias. The study was designed and conducted according to the Preferring Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Incidence, hazard, or odds ratios for AD comparing older adults with vs without a previous cancer diagnosis. In total, 19 cohort studies and 3 case-control studies of the associations between any cancer type (n = 13), prostate cancer (n = 5), breast cancer (n = 1), and nonmelanoma skin cancer (n = 3) with AD were identified, representing 9 630 435 individuals. In all studies combined, cancer was associated with decreased AD incidence (cohort studies: random-effects hazard ratio, 0.89; 95% CI, 0.79-1.00; case-control studies: random-effects odds ratio, 0.75; 95% CI, 0.61-0.93). Studies with insufficient or inappropriate confounder control or greater likelihood of AD diagnostic bias had mean hazard ratios closer to the null value, indicating that these biases could not explain the observed inverse association. Competing risks bias was rare. Studies with greater likelihood of survival bias had mean hazard ratios farther from the null value. The weak inverse association between cancer and AD may reflect shared inverse etiological mechanisms or survival bias but is not likely attributable to diagnostic bias, competing risks bias, or insufficient or inappropriate control for potential confounding factors. This systematic review and meta-analysis assesses the likelihood that methodological biases in cohort studies and case-control studies, rather than a common etiology, explain the inverse association between cancer and subsequent Alzheimer disease incidence among older adults.
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影响因子：
15.8
作者：
Moher D;Liberati A;Tetzlaff J;Altman DG;PRISMA Group
通讯作者：
PRISMA Group
影响因子：
5.4
作者：
Gianattasio, Kan Z.;Wu, Qiong;Power, Melinda C.
通讯作者：
Power, Melinda C.
影响因子：
7.7
作者：
Cheung, Yin Bun;Ma, Xiangmei;Milligan, Paul
通讯作者：
Milligan, Paul
DOI：
10.1093/geronb/gbw040
发表时间：
2017-11-01
影响因子：
6.2
作者：
Hanson, Heidi A.;Horn, Kevin P.;Smith, Ken R.
通讯作者：
Smith, Ken R.
影响因子：
4.2
作者：
Ma SL;Tang NL;Tam CW;Lui VW;Lam LC;Chiu HF;Driver JA;Pastorino L;Lu KP
通讯作者：
Lu KP