Article Text

Environmental risk factors for non-Hodgkin's lymphoma: umbrella review and comparison of meta-analyses of summary and individual participant data
  1. Xiaoting Shi1,
  2. Haoran Zhuo1,
  3. Yuxuan Du2,
  4. Kate Nyhan1,3,
  5. John Ioannidis4 and
  6. Joshua D Wallach1
  1. 1 Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA
  2. 2 Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA
  3. 3 Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT, USA
  4. 4 Department of Medicine, of Epidemiology and Population Health, of Biomedical Data Science, and of Statistics, and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA
  1. Correspondence to Dr Joshua D Wallach, Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA; joshua.wallach{at}yale.edu

Abstract

Objectives 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.

Design Umbrella review and comparison of meta-analyses of summary and individual participant level data.

Data sources Medline, Embase, Scopus, Web of Science Core Collection, Cochrane Library, and Epistemonikos, from inception to 23 July 2021.

Eligibility criteria for selecting studies 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).

Data extraction and synthesis 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, I2 <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.

Results 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.

Conclusion 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.

Review registration number PROSPERO CRD42020178010.

  • lymphoma
  • epidemiology

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Footnotes

  • Twitter @JoshuaDWallach

  • Contributors XS and JDW originally conceived this study. XS, JI, and JDW designed this study. XS, HZ, YD, KN, and JDW acquired the data. XS and YD conducted the statistical analysis. XS and JDW and drafted the manuscript. XS, JPAI, and JDW participated in the interpretation of the data. All authors and critically revised the manuscript for important intellectual content. XS and JDW had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. JDW provided supervision. JDW is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Transparency: The lead author (the guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Funding XS is supported by the China Scholarship Council. JDW is supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award K01AA028258.

  • Competing interests Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; in the past 36 months, JDW received research support from the US Food and Drug Administration and through Yale University from Johnson & Johnson to develop methods of clinical trial data sharing.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.