Systematic review of Mendelian randomization studies on risk of cancer
Abstract 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 genetical...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-022-02246-y |
| _version_ | 1798023941581701120 |
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| author | Georgios Markozannes Afroditi Kanellopoulou Olympia Dimopoulou Dimitrios Kosmidis Xiaomeng Zhang Lijuan Wang Evropi Theodoratou Dipender Gill Stephen Burgess Konstantinos K. Tsilidis |
| author_facet | Georgios Markozannes Afroditi Kanellopoulou Olympia Dimopoulou Dimitrios Kosmidis Xiaomeng Zhang Lijuan Wang Evropi Theodoratou Dipender Gill Stephen Burgess Konstantinos K. Tsilidis |
| author_sort | Georgios Markozannes |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T17:54:26Z |
| format | Article |
| id | doaj.art-857b36cbf839460cbebc0829d3618136 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-04-11T17:54:26Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-857b36cbf839460cbebc0829d36181362022-12-22T04:10:57ZengBMCBMC Medicine1741-70152022-02-0120112210.1186/s12916-022-02246-ySystematic review of Mendelian randomization studies on risk of cancerGeorgios Markozannes0Afroditi Kanellopoulou1Olympia Dimopoulou2Dimitrios Kosmidis3Xiaomeng Zhang4Lijuan Wang5Evropi Theodoratou6Dipender Gill7Stephen Burgess8Konstantinos K. Tsilidis9Department of Hygiene and Epidemiology, University of Ioannina School of MedicineDepartment of Hygiene and Epidemiology, University of Ioannina School of MedicineBristol Medical School, University of BristolDepartment of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of AthensCentre for Global Health, Usher Institute, The University of EdinburghCentre for Global Health, Usher Institute, The University of EdinburghCentre for Global Health, Usher Institute, The University of EdinburghDepartment of Epidemiology and Biostatistics, St. Mary’s Campus, School of Public Health, Imperial College LondonMedical Research Council Biostatistics Unit, University of CambridgeDepartment of Hygiene and Epidemiology, University of Ioannina School of MedicineAbstract 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.https://doi.org/10.1186/s12916-022-02246-yMendelian randomizationCancerRisk factorsSystematic reviewEvidence grading |
| spellingShingle | Georgios Markozannes Afroditi Kanellopoulou Olympia Dimopoulou Dimitrios Kosmidis Xiaomeng Zhang Lijuan Wang Evropi Theodoratou Dipender Gill Stephen Burgess Konstantinos K. Tsilidis Systematic review of Mendelian randomization studies on risk of cancer BMC Medicine Mendelian randomization Cancer Risk factors Systematic review Evidence grading |
| title | Systematic review of Mendelian randomization studies on risk of cancer |
| title_full | Systematic review of Mendelian randomization studies on risk of cancer |
| title_fullStr | Systematic review of Mendelian randomization studies on risk of cancer |
| title_full_unstemmed | Systematic review of Mendelian randomization studies on risk of cancer |
| title_short | Systematic review of Mendelian randomization studies on risk of cancer |
| title_sort | systematic review of mendelian randomization studies on risk of cancer |
| topic | Mendelian randomization Cancer Risk factors Systematic review Evidence grading |
| url | https://doi.org/10.1186/s12916-022-02246-y |
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