| Title: |
Genetic risk factors modulate the association between physical activity and colorectal cancer |
| Authors: |
Peoples, Anita R.; Obón Santacana, Mireia; Kim, Andre E.; Kawaguchi, Eric S.; Fu, Yubo; Qu, Conghui; Moratalla Navarro, Ferran; Morrison, John; Lin, Yi; Arndt, Volker; Berndt, Sonja I.; Bien, Stephanie A.; Bishop, D. Timothy; Bouras, Emmanouil; Brenner, Hermann; Buchanan, Daniel D; Campbell, Peter T.; Chan, Andrew T.; Chang-Claude, Jenny; Conti, David V.; Corley, Douglas A.; Devall, Matthew A.; Dimou, Niki; Drew, David A.; Gruber, Stephen B.; Gunter, Marc J.; Harlid, Sophia; Harrison, Tabitha A.; Hoffmeister, Michael; Hsu, Li; Huyghe, Jeroen R.; Keku, Temitope O.; Kundaje, Anshul; Lewinger, Juan Pablo; Li, Li; Lynch, Brigid M.; Le Marchand, Loïc; Martín, Vicente; Murphy, Neil; Newton, Christina C.; Ogino, Shuji; Hardikar, Sheetal; Ose, Jennifer; Pai, Rish K.; Palmer, Julie R.; Papadimitriou, Nikos; Pardamean, Bens; Pellatt, Andrew J.; Pinchev, Mila; Platz, Elizabeth A.; Potter, John D.; Rennert, Gad; Ruiz-Narvaez, Edward; Sakoda, Lori C.; Schoen, Robert E.; Shcherbina, Anna; Stern, Marianna C.; Su, Yu-Ru; Thomas, Claire E.; Tian, Yu; Tsilidis, Konstantinos K.; Um, Caroline; van Duijnhoven, Franzel J.B.; Van Guelpen, Bethany; Visvanathan, Kala; Wang, Junzhi; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Ulrich, Cornelia M.; Peters, Ulrike; Gauderman, W. James; Moreno Aguado, Víctor |
| Publisher Information: |
BioMed Central |
| Publication Year: |
2026 |
| Collection: |
Dipòsit Digital de la Universitat de Barcelona |
| Subject Terms: |
Càncer colorectal; Exercici; Colorectal cancer; Exercise |
| Description: |
Background: Physical activity is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene–physical activity interaction analysis. Methods: Using logistic regression (1-d.f), two-step screening and testing method (EDGE), and joint tests (3-d.f), we analyzed interactions between common genetic variants across the genome and physical activity in relation to CRC risk. Self-reported physical activity levels were categorized as active (≥ 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk; 39,992 participants) and as study- and sex-specific quartiles of activity (42,602 participants). Results: Physical activity was inversely associated with CRC risk overall (OR [active vs. inactive] = 0.85; 95% CI = 0.81–0.90). The two-step EDGE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and physical activity for CRC risk (p-interaction = 2.6 × 10−8). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95% CI = 0.75–0.85), but no significant physical activity–CRC associations among CT or TT carriers. When physical activity was modeled as quartiles, the 1-d.f. test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between physical activity and CRC (p-interaction = 3.5 × 10−8). Stratification at this locus showed that an increase in physical activity (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95% CI = 0.72–0.82). Conclusions: In summary, we identified two genetic variants that modified the association between physical activity and CRC risk. One of them, related to GREM1 and SCG5, suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be involved in the protective association between ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
17 p.; application/pdf |
| Language: |
English |
| ISSN: |
41645200 |
| Relation: |
Reproducció del document publicat a: https://doi.org/10.1186/s12916-026-04675-5; BMC Medicine, 2026, vol. 4; https://doi.org/10.1186/s12916-026-04675-5; https://hdl.handle.net/2445/230574; 767742 |
| Availability: |
https://hdl.handle.net/2445/230574 |
| Rights: |
cc-by-nc-nd (c) Peoples, AR. et al., 2026 ; http://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.71804C8C |
| Database: |
BASE |