Shi Xiaoting, Zhuo Haoran, Du Yuxuan, Nyhan Kate, Ioannidis John, Wallach Joshua D
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA.
BMJ Med. 2022 Jun 27;1(1):e000184. doi: 10.1136/bmjmed-2022-000184. eCollection 2022.
To summarise the range, strength, and validity of reported associations between environmental risk factors and non-Hodgkin's lymphoma, and to evaluate the concordance between associations reported in meta-analyses of summary level data and meta-analyses of individual participant data.
Umbrella review and comparison of meta-analyses of summary and individual participant level data.
Medline, Embase, Scopus, Web of Science Core Collection, Cochrane Library, and Epistemonikos, from inception to 23 July 2021.
English language meta-analyses of summary level data and of individual participant data evaluating associations between environmental risk factors and incident non-Hodgkin's lymphoma (overall and subtypes).
Summary effect estimates from meta-analyses of summary level data comparing ever versus never exposure that were adjusted for the largest number of potential confounders were re-estimated using a random effects model and classified as presenting evidence that was non-significant, weak (P<0.05), suggestive (P<0.001 and >1000 cases), highly suggestive (P<0.000001, >1000 cases, largest study reporting a significant association), or convincing (P<0.000001, >1000 cases, largest study reporting a significant association, I <50%, 95% prediction interval excluding the null value, and no evidence of small study effects and excess significance bias) evidence. When the same exposures, exposure contrast levels, and outcomes were evaluated in meta-analyses of summary level data and meta-analyses of individual participant data from the International Lymphoma Epidemiology (InterLymph) Consortium, concordance in terms of direction, level of significance, and overlap of 95% confidence intervals was examined. Methodological quality of the meta-analyses of summary level data was assessed by the AMSTAR 2 tool.
We identified 85 meta-analyses of summary level data reporting 257 associations for 134 unique environmental risk factors and 10 subtypes of non-Hodgkin's lymphoma nearly all (79, 93%) were classified as having critically low quality. Most associations (225, 88%) presented either non-significant or weak evidence. The 11 (4%) associations presenting highly suggestive evidence were primarily for autoimmune or infectious disease related risk factors. Only one association, between history of coeliac disease and risk of non-Hodgkin's lymphoma, presented convincing evidence. Of 40 associations reported in meta-analyses of summary level data that were also evaluated in InterLymph meta-analyses of individual participant data, 22 (55%) pairs were in the same direction, had the same level of statistical significance, and had overlapping 95% confidence intervals; 28 (70%) pairs had summary effect sizes from the meta-analyses of individual participant data that were more conservative.
This umbrella review suggests evidence of many meta-analyses of summary level data reporting weak associations between environmental risk factors and non-Hodgkin's lymphoma. Improvements to primary studies as well as evidence synthesis in evaluations of evironmental risk factors and non-Hodgkin's lymphoma are needed.
PROSPERO CRD42020178010.
总结已报道的环境危险因素与非霍奇金淋巴瘤之间关联的范围、强度和有效性，并评估汇总水平数据的荟萃分析与个体参与者数据的荟萃分析中所报道关联之间的一致性。
对汇总水平数据和个体参与者水平数据的荟萃分析进行伞状综述和比较。
从创刊至2021年7月23日的Medline、Embase、Scopus、科学网核心合集、考克兰图书馆和Epistemonikos。
评估环境危险因素与新发非霍奇金淋巴瘤（总体及亚型）之间关联的英文汇总水平数据和个体参与者数据的荟萃分析。
使用随机效应模型重新估计汇总水平数据荟萃分析中比较曾经暴露与从未暴露且针对最多潜在混杂因素进行调整后的汇总效应估计值，并将其分类为呈现非显著、弱（P<0.05）、提示性（P<0.001且病例数>1000）、高度提示性（P<0.000001，病例数>1000，最大研究报告有显著关联）或令人信服（P<0.000001，病例数>1000，最大研究报告有显著关联，I²<50%，95%预测区间不包括无效值，且无小研究效应和过度显著性偏倚证据）的证据。当在汇总水平数据的荟萃分析和国际淋巴瘤流行病学（InterLymph）联盟的个体参与者数据的荟萃分析中评估相同的暴露、暴露对比水平和结局时，检查方向、显著性水平和95%置信区间重叠方面的一致性。汇总水平数据的荟萃分析的方法学质量通过AMSTAR 2工具进行评估。
我们识别出85项汇总水平数据的荟萃分析，报告了134种独特环境危险因素与10种非霍奇金淋巴瘤亚型之间的257种关联，几乎所有（79项，93%）被归类为质量极低。大多数关联（225项，88%）呈现非显著或弱证据。呈现高度提示性证据的11项（4%）关联主要针对自身免疫或感染性疾病相关危险因素。只有一项关联，即乳糜泻病史与非霍奇金淋巴瘤风险之间的关联，呈现令人信服证据。在汇总水平数据的荟萃分析中报告且也在InterLymph个体参与者数据的荟萃分析中评估的40项关联中，22对（55%）在方向上相同、具有相同的统计显著性水平且95%置信区间重叠；28对（70%）在个体参与者数据的荟萃分析中的汇总效应大小更为保守。
这项伞状综述表明，许多汇总水平数据的荟萃分析有证据显示环境危险因素与非霍奇金淋巴瘤之间存在弱关联。在环境危险因素与非霍奇金淋巴瘤的评估中，需要改进原始研究以及证据综合分析。
PROSPERO CRD42020178010。
