Identification of potential mediators of the relationship between body mass index and colorectal cancer: a Mendelian randomization analysis

  1. Bouras, Emmanouil ORCID logo
  2. Gill, Dipender ORCID logo
  3. Zuber, Verena ORCID logo
  4. Murphy, Neil ORCID logo
  5. Dimou, Niki
  6. Aleksandrova, Krasimira ORCID logo
  7. Lewis, Sarah J.
  8. Martin, Richard M.
  9. Yarmolinsky, James
  10. Albanes, Demetrius
  11. Brenner, Hermann
  12. Castellví-Bel, Sergi
  13. Chan, Andrew T.
  14. Cheng, Iona ORCID logo
  15. Gruber, Stephen B.
  16. Van Guelpen, Bethany ORCID logo
  17. Li, Christopher I.
  18. Le Marchand, Loic
  19. Newcomb, Polly A.
  20. Ogino, Shuji
  21. Pellatt, Andrew
  22. Schmit, Stephanie L.
  23. Wolk, Alicja ORCID logo
  24. Wu, Anna H.
  25. Peters, Ulrike
  26. Gunter, Marc J.
  27. Tsilidis, Konstantinos K.

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WeightNameValue
1000 Titel
  • Identification of potential mediators of the relationship between body mass index and colorectal cancer: a Mendelian randomization analysis
1000 Autor/in
  1. Bouras, Emmanouil |
  2. Gill, Dipender |
  3. Zuber, Verena |
  4. Murphy, Neil |
  5. Dimou, Niki |
  6. Aleksandrova, Krasimira |
  7. Lewis, Sarah J. |
  8. Martin, Richard M. |
  9. Yarmolinsky, James |
  10. Albanes, Demetrius |
  11. Brenner, Hermann |
  12. Castellví-Bel, Sergi |
  13. Chan, Andrew T. |
  14. Cheng, Iona |
  15. Gruber, Stephen B. |
  16. Van Guelpen, Bethany |
  17. Li, Christopher I. |
  18. Le Marchand, Loic |
  19. Newcomb, Polly A. |
  20. Ogino, Shuji |
  21. Pellatt, Andrew |
  22. Schmit, Stephanie L. |
  23. Wolk, Alicja |
  24. Wu, Anna H. |
  25. Peters, Ulrike |
  26. Gunter, Marc J. |
  27. Tsilidis, Konstantinos K. |
1000 Erscheinungsjahr 2024
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-05-09
1000 Erschienen in
1000 Quellenangabe
  • 53(3):dyae067
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1093/ije/dyae067 |
  • https://pmc.ncbi.nlm.nih.gov/articles/PMC11082423/ |
1000 Ergänzendes Material
  • https://academic.oup.com/ije/article/53/3/dyae067/7667948#449570185 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • BACKGROUND: Colorectal cancer (CRC) is the third-most-common cancer worldwide and its rates are increasing. Elevated body mass index (BMI) is an established risk factor for CRC, although the molecular mechanisms behind this association remain unclear. Using the Mendelian randomization (MR) framework, we aimed to investigate the mediating effects of putative biomarkers and other CRC risk factors in the association between BMI and CRC. METHODS: We selected as mediators biomarkers of established cancer-related mechanisms and other CRC risk factors for which a plausible association with obesity exists, such as inflammatory biomarkers, glucose homeostasis traits, lipids, adipokines, insulin-like growth factor 1 (IGF1), sex hormones, 25-hydroxy-vitamin D, smoking, physical activity (PA) and alcohol consumption. We used inverse-variance weighted MR in the main univariable analyses and performed sensitivity analyses (weighted-median, MR–Egger, Contamination Mixture). We used multivariable MR for the mediation analyses. RESULTS: Genetically predicted BMI was positively associated with CRC risk [odds ratio per SD (5 kg/m2) = 1.17, 95% CI: 1.08–1.24, P-value = 1.4 × 10−5] and robustly associated with nearly all potential mediators. Genetically predicted IGF1, fasting insulin, low-density lipoprotein cholesterol, smoking, PA and alcohol were associated with CRC risk. Evidence for attenuation was found for IGF1 [explained 7% (95% CI: 2–13%) of the association], smoking (31%, 4–57%) and PA (7%, 2–11%). There was little evidence for pleiotropy, although smoking was bidirectionally associated with BMI and instruments were weak for PA. CONCLUSIONS: The effect of BMI on CRC risk is possibly partly mediated through plasma IGF1, whereas the attenuation of the BMI–CRC association by smoking and PA may reflect confounding and shared underlying mechanisms rather than mediation.
1000 Sacherschließung
lokal Mendelian randomization
lokal colorectal cancer
lokal mediation analysis
lokal Body mass index
lokal BMI
lokal CRC
lokal obesity
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-1489-5506|https://orcid.org/0000-0001-7312-7078|https://orcid.org/0000-0001-9827-1877|https://orcid.org/0000-0003-3347-8249|https://frl.publisso.de/adhoc/uri/RGltb3UsIE5pa2k=|https://orcid.org/0000-0002-1275-1827|https://frl.publisso.de/adhoc/uri/TGV3aXMsIFNhcmFoIEou|https://frl.publisso.de/adhoc/uri/TWFydGluLCBSaWNoYXJkIE0u|https://frl.publisso.de/adhoc/uri/WWFybW9saW5za3ksIEphbWVz|https://frl.publisso.de/adhoc/uri/QWxiYW5lcywgRGVtZXRyaXVz|https://frl.publisso.de/adhoc/uri/QnJlbm5lciwgSGVybWFubg==|https://frl.publisso.de/adhoc/uri/Q2FzdGVsbHbDrS1CZWwsIFNlcmdp|https://frl.publisso.de/adhoc/uri/Q2hhbiwgQW5kcmV3IFQu|https://orcid.org/0000-0003-4132-2893|https://frl.publisso.de/adhoc/uri/R3J1YmVyLCBTdGVwaGVuIEIu|https://orcid.org/0000-0002-9692-101X|https://frl.publisso.de/adhoc/uri/TGksIENocmlzdG9waGVyIEku|https://frl.publisso.de/adhoc/uri/TGUgTWFyY2hhbmQsIExvaWM=|https://frl.publisso.de/adhoc/uri/TmV3Y29tYiwgUG9sbHkgQS4=|https://frl.publisso.de/adhoc/uri/T2dpbm8sIFNodWpp|https://frl.publisso.de/adhoc/uri/UGVsbGF0dCwgQW5kcmV3|https://frl.publisso.de/adhoc/uri/U2NobWl0LCBTdGVwaGFuaWUgTC4=|https://orcid.org/0000-0001-7387-6845|https://frl.publisso.de/adhoc/uri/V3UsIEFubmEgSC4=|https://frl.publisso.de/adhoc/uri/UGV0ZXJzLCBVbHJpa2U=|https://frl.publisso.de/adhoc/uri/R3VudGVyLCBNYXJjIEou|https://frl.publisso.de/adhoc/uri/VHNpbGlkaXMsIEtvbnN0YW50aW5vcyBLLg==
1000 Label
1000 Förderer
  1. Cancer Research UK |
  2. National Institute for Health |
  3. Cancer Research UK 25 |
  4. NIHR Bristol Biomedical Research Centre |
  5. Medical Research Council |
1000 Fördernummer
  1. PPRCPJT\100005; C68933/A28534
  2. NIHR202411
  3. C18281/A29019
  4. BRC-1215–20011
  5. MC_UU_00011/1; MC_UU_00011/3; MC_UU_00011/6; MC_UU_00011/4
1000 Förderprogramm
  1. -
  2. -
  3. -
  4. -
  5. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Cancer Research UK |
    1000 Förderprogramm -
    1000 Fördernummer PPRCPJT\100005; C68933/A28534
  2. 1000 joinedFunding-child
    1000 Förderer National Institute for Health |
    1000 Förderprogramm -
    1000 Fördernummer NIHR202411
  3. 1000 joinedFunding-child
    1000 Förderer Cancer Research UK 25 |
    1000 Förderprogramm -
    1000 Fördernummer C18281/A29019
  4. 1000 joinedFunding-child
    1000 Förderer NIHR Bristol Biomedical Research Centre |
    1000 Förderprogramm -
    1000 Fördernummer BRC-1215–20011
  5. 1000 joinedFunding-child
    1000 Förderer Medical Research Council |
    1000 Förderprogramm -
    1000 Fördernummer MC_UU_00011/1; MC_UU_00011/3; MC_UU_00011/6; MC_UU_00011/4
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6488835.rdf
1000 Erstellt am 2024-11-01T11:02:41.161+0100
1000 Erstellt von 266
1000 beschreibt frl:6488835
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet 2024-11-04T10:01:13.518+0100
1000 Objekt bearb. Mon Nov 04 10:01:03 CET 2024
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1000 Oai Id
  1. oai:frl.publisso.de:frl:6488835 |
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