Body size and risk of colorectal cancer molecular defined subtypes and pathways : mendelian randomization analyses

Papadimitriou, Nikos; Qu, Conghui; Harrison, Tabitha A.; Bever, Alaina M.; Martin, Richard M.; Tsilidis, Konstantinos K.; Newcomb, Polly A.; Thibodeau, Stephen N.; Newton, Christina C.; Um, Caroline Y.; Obón-Santacana, Mireia; Moreno, Victor; Brenner, Hermann; Mandic, Marko; Chang-Claude, Jenny; Hoffmeister, Michael; Pellatt, Andrew J.; Schoen, Robert E.; Harlid, Sophia; Ogino, Shuji; Ugai, Tomotaka; Buchanan, Daniel D.; Lynch, Brigid M.; Gruber, Stephen B.; Cao, Yin; Hsu, Li; Huyghe, Jeroen R.; Lin, Yi; Steinfelder, Robert S.; Sun, Wei; van Guelpen, Bethany; Zaidi, Syed H.; Toland, Amanda E.; Berndt, Sonja I.; Huang, Wen-Yi; Aglago, Elom K.; Drew, David A.; French, Amy J.; Georgeson, Peter; Giannakis, Marios; Hullar, Meredith; Nowak, Johnathan A.; Thomas, Claire E.; Le Marchand, Loic; Cheng, Iona; Gallinger, Steven; Jenkins, Mark A.; Gunter, Marc J.; Campbell, Peter T.; Peters, Ulrike; Song, Mingyang; Phipps, Amanda I.; Murphy, Neil

umu.sePublications

System disruptions

We are currently experiencing disruptions on the search portals due to high traffic. We are working to resolve the issue, you may temporarily encounter an error message.

Simple search

Advanced search -
Research publications Advanced search -
Student theses Statistics

English Svenska Norsk

Change search

Cite ExportLink to record

Permanent link

https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-222809

Direct link

https://umu.diva-portal.org/smash/record.jsf?pid=diva2:1850826

Cite

Citation style

apa
apa-6th-edition.csl
ieee
modern-language-association-8th-edition
vancouver
Other style

More styles

Language

de-DE
en-GB
en-US
fi-FI
nn-NO
nn-NB
sv-SE
Other locale

More languages

Output format

html
text
asciidoc
rtf

Body size and risk of colorectal cancer molecular defined subtypes and pathways: mendelian randomization analyses

Papadimitriou, Nikos

Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.

Qu, Conghui

Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.

Harrison, Tabitha A.

Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.

Bever, Alaina M.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, MA, Boston, United States.

Martin, Richard M.

MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, United Kingdom; National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, United Kingdom.

Tsilidis, Konstantinos K.

Newcomb, Polly A.

Thibodeau, Stephen N.

Newton, Christina C.

Um, Caroline Y.

Obón-Santacana, Mireia

Moreno, Victor

Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine and Health Sciences and Universitat de Barcelona Institute of Complex Systems (UBICS), University of Barcelona (UB), L'Hospitalet de Llobregat, Barcelona, Spain.

Brenner, Hermann

Mandic, Marko

Chang-Claude, Jenny

Hoffmeister, Michael

Pellatt, Andrew J.

Schoen, Robert E.

Harlid, Sophia

Ogino, Shuji

Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States; Cancer Immunology Program, Dana-Farber Harvard Cancer Center, MA, Boston, United States; Broad Institute of MIT and Harvard, MA, Cambridge, United States.

Ugai, Tomotaka

Buchanan, Daniel D.

Lynch, Brigid M.

Gruber, Stephen B.

Cao, Yin

Hsu, Li

Huyghe, Jeroen R.

Lin, Yi

Steinfelder, Robert S.

Sun, Wei

van Guelpen, Bethany

Zaidi, Syed H.

Toland, Amanda E.

Berndt, Sonja I.

Huang, Wen-Yi

Aglago, Elom K.

Drew, David A.

French, Amy J.

Georgeson, Peter

Giannakis, Marios

Hullar, Meredith

Nowak, Johnathan A.

Thomas, Claire E.

Le Marchand, Loic

Cheng, Iona

Gallinger, Steven

Jenkins, Mark A.

Gunter, Marc J.

Campbell, Peter T.

Peters, Ulrike

Song, Mingyang

Phipps, Amanda I.

Murphy, Neil

Show others and affiliations

2024 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 101, article id 105010Article in journal (Refereed) Published

Abstract [en]

Background: Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.

Methods: We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).

Findings: A 1-standard deviation (SD:5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10−5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10−5) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03).

Interpretation: Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4).

Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.

Place, publisher, year, edition, pages

Elsevier, 2024. Vol. 101, article id 105010

Keywords [en]

Colorectal cancer, Mendelian randomization, Molecular subtypes, Obesity

National Category

Cancer and Oncology

Identifiers

URN: urn:nbn:se:umu:diva-222809DOI: 10.1016/j.ebiom.2024.105010PubMedID: 38350331Scopus ID: 2-s2.0-85184797654OAI: oai:DiVA.org:umu-222809DiVA, id: diva2:1850826

Funder

Swedish Research Council, VR 2017-00650Swedish Research Council, VR 2017-01737Knut and Alice Wallenberg Foundation, VLL-765961Available from: 2024-04-11 Created: 2024-04-11 Last updated: 2024-04-11Bibliographically approved

Open Access in DiVA

fulltext(442 kB)

56 downloads

File information

File name FULLTEXT01.pdfFile size 442 kBChecksum SHA-512

5b1da60285d320745c9adc7c4603a89d3b3dec846f15f1d02fd6abf1ceac9b66b4566292eb683127e23984aa6c5266236d74fdf3b51f2edb9e609f1a45472d55

Type fulltextMimetype application/pdf

Authority records

Harlid, Sophia van Guelpen, Bethany

Search in DiVA

Total: 56 downloads

The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi

pubmed

urn-nbn

Total: 284 hits