Systematic review of Mendelian randomization studies on risk of cancer
Authors
Markozannes, Georgios
Kanellopoulou, Afroditi
Dimopoulou, Olympia
Kosmidis, Dimitrios
Zhang, Xiaomeng
Wang, Lijuan
Theodoratou, Evropi
Gill, Dipender
Tsilidis, Konstantinos K
Publication Date
2022-12Journal Title
BMC Medicine
Publisher
Springer Science and Business Media LLC
Volume
20
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Markozannes, G., Kanellopoulou, A., Dimopoulou, O., Kosmidis, D., Zhang, X., Wang, L., Theodoratou, E., et al. (2022). Systematic review of Mendelian randomization studies on risk of cancer. BMC Medicine, 20 (1) https://doi.org/10.1186/s12916-022-02246-y
Abstract
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>We aimed to map and describe the current state of Mendelian randomization (MR) literature on cancer risk and to identify associations supported by robust evidence.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>We searched PubMed and Scopus up to 06/10/2020 for MR studies investigating the association of any genetically predicted risk factor with cancer risk. We categorized the reported associations based on a priori designed levels of evidence supporting a causal association into four categories, namely <jats:italic>robust</jats:italic>, <jats:italic>probable</jats:italic>, <jats:italic>suggestive</jats:italic>, and <jats:italic>insufficient</jats:italic>, based on the significance and concordance of the main MR analysis results and at least one of the MR-Egger, weighed median, MRPRESSO, and multivariable MR analyses. Associations not presenting any of the aforementioned sensitivity analyses were not graded.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>We included 190 publications reporting on 4667 MR analyses. Most analyses (3200; 68.6%) were not accompanied by any of the assessed sensitivity analyses. Of the 1467 evaluable analyses, 87 (5.9%) were supported by <jats:italic>robust</jats:italic>, 275 (18.7%) by <jats:italic>probable</jats:italic>, and 89 (6.1%) by <jats:italic>suggestive</jats:italic> evidence. The most prominent <jats:italic>robust</jats:italic> associations were observed for anthropometric indices with risk of breast, kidney, and endometrial cancers; circulating telomere length with risk of kidney, lung, osteosarcoma, skin, thyroid, and hematological cancers; sex steroid hormones and risk of breast and endometrial cancer; and lipids with risk of breast, endometrial, and ovarian cancer.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Despite the large amount of research on genetically predicted risk factors for cancer risk, limited associations are supported by robust evidence for causality. Most associations did not present a MR sensitivity analysis and were thus non-evaluable. Future research should focus on more thorough assessment of sensitivity MR analyses and on more transparent reporting.</jats:p>
</jats:sec>
Keywords
Research Article, Mendelian randomization, Cancer, Risk factors, Systematic review, Evidence grading
Sponsorship
Cancer research UK (C18281/A29019)
Wellcome Trust (204623/Z/16/Z)
NIHR Cambridge Biomedical Research Centre (BRC-1215-20014)
Cancer Research UK Career Development Fellowship (C31250/A22804)
Identifiers
s12916-022-02246-y, 2246
External DOI: https://doi.org/10.1186/s12916-022-02246-y
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333563
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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