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dc.contributor.authorMarkozannes, Georgios
dc.contributor.authorKanellopoulou, Afroditi
dc.contributor.authorDimopoulou, Olympia
dc.contributor.authorKosmidis, Dimitrios
dc.contributor.authorZhang, Xiaomeng
dc.contributor.authorWang, Lijuan
dc.contributor.authorTheodoratou, Evropi
dc.contributor.authorGill, Dipender
dc.contributor.authorBurgess, Stephen
dc.contributor.authorTsilidis, Konstantinos K
dc.date.accessioned2022-01-12T00:30:44Z
dc.date.available2022-01-12T00:30:44Z
dc.date.issued2022-02-02
dc.identifier.issn1741-7015
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332636
dc.description.abstractBACKGROUND: 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.
dc.publisherBioMed Central
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleSystematic review of Mendelian randomization studies on risk of cancer.
dc.typeArticle
dc.publisher.departmentMrc Biostatistics Unit
dc.date.updated2022-01-10T17:07:25Z
prism.publicationNameBMC Med
dc.identifier.doi10.17863/CAM.80081
dcterms.dateAccepted2022-01-10
rioxxterms.versionofrecord10.1186/s12916-022-02246-y
rioxxterms.versionAM
dc.contributor.orcidBurgess, Stephen [0000-0001-5365-8760]
dc.identifier.eissn1741-7015
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (204623/Z/16/Z)
pubs.funder-project-idNational Institute for Health Research (NIHRDH-IS-BRC-1215-20014)
cam.orpheus.successThu Feb 24 18:06:39 GMT 2022 - Embargo updated
cam.orpheus.counter1
cam.depositDate2022-01-10
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2022-02-02


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International