Physical activity and molecular subtypes of colorectal cancer: a pooled observational analysis and Mendelian randomization study

Background Physical activity is associated with lower colorectal cancer (CRC) risk, but its association with molecular subtypes defined by genetic and epigenetic alterations of the disease is unclear. Such information may enhance the understanding of the mechanisms related to the benefits of physica...

Descripción completa

Detalles Bibliográficos
Autores: Chalitsios, Christos V., Markozannes, Georgios, Aglago, Elom K., Berndt, Sonja I., Buchanan, Daniel D., Campbell, Peter T., Cao, Yin, Chan, Andrew T., Dimou, Niki, Drew, David A., French, Amy J., Georgeson, Peter, Giannakis, Marios, Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hoffmeister, Michael, Hsu, Li, Huang, Wen Yi, Aj Hullar, Meredith, Huyghe, Jeroen R., Lynch, Brigid M., Moreno Aguado, Víctor, Murphy, Neil, Newton, Christina C., Nowak, Jonathan A., Obón Santacana, Mireia, Ogino, Shuji, Qu, Conghui, Schmit, Stephanie L., Steinfelder, Robert S., Sun, Wei, Thomas, Claire E., Toland, Amanda E., Trinh, Quang M., Ugai, Tomotaka, Um, Caroline Y., Van Guelpen, Bethany, Zaidi, Syed H., Schoen, Robert E., Woods, Michael O., Brenner, Hermann, Andreson, Laura, Pellatt, Andrew J., Peters, Ulrike, Phipps, Amanda I., Tsilidis, Konstantinos K.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/224983
Acceso en línea:https://hdl.handle.net/2445/224983
Access Level:acceso abierto
Palabra clave:Marcadors tumorals
Genètica mèdica
Càncer colorectal
Tumor markers
Medical genetics
Colorectal cancer
Descripción
Sumario:Background Physical activity is associated with lower colorectal cancer (CRC) risk, but its association with molecular subtypes defined by genetic and epigenetic alterations of the disease is unclear. Such information may enhance the understanding of the mechanisms related to the benefits of physical activity.Methods Pooled observational (cases: n = 5386; controls: n = 6798; studies n = 5) and genome-wide association data (cases: n = 8178; controls: n = 10 472; studies n = 5) were used. We used multivariable logistic regression models and Mendelian randomization to assess the association between physical activity and the risk of CRC subtypes defined by individual tumor markers (and marker combinations), namely microsatellite instability status, CpG island methylator phenotype status, and BRAF and KRAS mutations. We used case-only analysis to test for differences between molecular subtypes. We applied Bonferroni correction to account for multiple tests.Results In the pooled observational analysis, higher levels of physical activity were associated with lower CRC risk (Obs-per 1SD, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.90 to 0.97), with an association that was stronger in males (Obs-per 1SD, OR = 0.91, 95% CI = 0.87 to 0.96) than in females (Obs-per 1SD, OR = 0.97, 95% CI = 0.91 to 1.03; Pinteraction = .04). Higher physical activity was associated with a lower risk of CRC across all molecular subtypes, especially in males. There was no difference in the associations by subtypes by pooled observational or Mendelian randomization analyses. The findings did not differ by study design, anatomical site, and early or late age onset of CRC.Conclusions Our findings suggest that physical activity is not differentially associated with the 4 major molecular subtypes involved in colorectal carcinogenesis, indicating that its benefits extend broadly across colorectal cancer pathogenesis.

Similares en LA Referencia