Systematic review of Mendelian randomization studies on risk of cancer.
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Tsilidis, Konstantinos K
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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 Med https://doi.org/10.1186/s12916-022-02246-y
BACKGROUND: 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. METHODS: 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 robust, probable, suggestive, and insufficient, 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. RESULTS: 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 robust, 275 (18.7%) by probable, and 89 (6.1%) by suggestive evidence. The most prominent robust 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. CONCLUSIONS: 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.
Cancer, Evidence grading, Mendelian randomization, Risk factors, Systematic review, Causality, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Risk Factors
Wellcome Trust (204623/Z/16/Z)
National Institute for Health Research (IS-BRC-1215-20014)
External DOI: https://doi.org/10.1186/s12916-022-02246-y
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332636
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/
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