TY  - JOUR
AU  - Bouras, Emmanouil
AU  - Yu, Ren
AU  - Kim, Andre E
AU  - Markozannes, Georgios
AU  - Murphy, Neil
AU  - Albanes, Demetrius
AU  - Anderson, Laura N
AU  - Barry, Elizabeth L
AU  - Berndt, Sonja I
AU  - Bishop, D Timothy
AU  - Brenner, Hermann
AU  - Burnett-Hartman, Andrea
AU  - Campbell, Peter T
AU  - Carreras-Torres, Robert
AU  - Chan, Andrew T
AU  - Cheng, Iona
AU  - Devall, Matthew A
AU  - Diez-Obrero, Virginia
AU  - Dimou, Niki
AU  - Drew, David A
AU  - Gruber, Stephen B
AU  - Gsur, Andrea
AU  - Hoffmeister, Michael
AU  - Hsu, Li
AU  - Huyghe, Jeroen R
AU  - Kawaguchi, Eric
AU  - Keku, Temitope O
AU  - Kundaje, Anshul
AU  - Küry, Sébastien
AU  - Le Marchand, Loïc
AU  - Lewinger, Juan Pablo
AU  - Li, Li
AU  - Lynch, Brigid M
AU  - Moreno, Victor
AU  - Morrison, John L
AU  - Newton, Christina C
AU  - Obón-Santacana, Mireia
AU  - Palmer, Julie R
AU  - Papadimitriou, Nikos
AU  - Pellatt, Andrew J
AU  - Peoples, Anita R
AU  - Pharoah, Paul D P
AU  - Platz, Elizabeth A
AU  - Qu, Conghui
AU  - Ruiz-Narvaez, Edward
AU  - Mendez, Joel Sanchez
AU  - Schoen, Robert E
AU  - Stern, Mariana C
AU  - Thomas, Claire E
AU  - Tian, Yu
AU  - Um, Caroline Y
AU  - Visvanathan, Kala
AU  - Vodicka, Pavel
AU  - Vymetalkova, Veronika
AU  - White, Emily
AU  - Wolk, Alicja
AU  - Woods, Michael O
AU  - Wu, Anna H
AU  - Gunter, Marc J
AU  - Gauderman, W James
AU  - Peters, Ulrike
AU  - Evangelou, Marina
AU  - Tsilidis, Konstantinos K
TI  - Using gene-environment interactions to explore pathways for colorectal cancer risk.
JO  - EBioMedicine
VL  - 121
SN  - 2352-3964
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DKFZ-2025-02094
SP  - 105964
PY  - 2025
AB  - Colorectal cancer (CRC) is a significant public health concern, highlighting the critical need for identifying novel intervention targets for its prevention.We conducted genome-wide interaction analyses for 15 exposures with established or putative CRC risk [body mass index (BMI), height, physical activity, smoking, type 2 diabetes, use of menopausal hormone therapy, non-steroidal anti-inflammatory drugs, and intake of alcohol, calcium, fibre, folate, fruits, processed meat, red meat, and vegetables], and used interaction estimates to explore pathways and genes underlying CRC risk. The adaptive combination of Bayes Factors (ADABF), and over-representation analysis (ORA) were used for pathway analyses, and findings were further investigated using publicly available resources [hallmarks of cancer, Open Targets Platform (OTP)].A total of 1973 pathways using ADABF, and 840 pathways using ORA, out of the 2950 analysed, were enriched (P < 0.05) for at least one exposure, as well as 1227 genes within the enriched pathways. Data were available for 811/1227 coding genes in the OTP, 241 of which were supported by strong relative abundance of prior evidence (overall OTP score > 0.05). Fifty percent of the genes (617/1227) mapped to at least one hallmark of cancer, most of which (388/617) pertained to the Sustaining Proliferative Signalling hallmark. Our findings reflect previously established pathways for CRC risk and highlight the emerging importance of several less studied genes. Common pathways were found for several combinations of exposures, potentially suggesting common underlying mechanisms.The results of the present analysis provide a basis for further functional research. If confirmed, they may help elucidate the etiological associations between risk factors and CRC risk and ultimately inform personalized prevention strategies.This study was funded by Cancer Research UK (CRUK; grant number:PPRCPJT∖100005) and World Cancer Research Fund International (WCRF; IIG_FULL_2020_022). Funding for grant IIG_FULL_2020_022 was obtained from Wereld Kanker Onderzoek Fonds (WKOF) as part of the World Cancer Research Fund International grant programme. Full funding details for the individual consortia are provided in the acknowledgements.
KW  - Colorectal cancer (Other)
KW  - Gene-environment interactions (Other)
KW  - Mechanisms (Other)
KW  - Molecular pathways (Other)
KW  - Pathway analysis (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41076992
DO  - DOI:10.1016/j.ebiom.2025.105964
UR  - https://inrepo02.dkfz.de/record/305350
ER  -