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Using gene-environment interactions to explore pathways for colorectal cancer risk
Emmanouil Bouras1, Ren Yu2, Andre E Kim3
1Department of Epidemiology and Biostatistics, School of Public Health-Faculty of Medicine, Imperial College London, London, UK; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
Ebiomedicine
|October 12, 2025
Summary
This study identified novel genes and pathways linked to colorectal cancer (CRC) risk by analyzing genome-wide interactions with 15 risk factors. Findings may inform personalized CRC prevention strategies.
Area of Science:
- Genomics
- Cancer Research
- Epidemiology
Background:
- Colorectal cancer (CRC) poses a significant public health challenge.
- Identifying novel intervention targets is crucial for CRC prevention.
Purpose of the Study:
- To conduct genome-wide interaction analyses for 15 exposures and CRC risk.
- To explore pathways and genes underlying CRC risk using interaction estimates.
Main Methods:
- Genome-wide interaction analyses were performed for 15 CRC risk factors.
- Adaptive combination of Bayes Factors (ADABF) and over-representation analysis (ORA) were used for pathway analyses.
- Findings were investigated using the Open Targets Platform (OTP) and cancer hallmarks.
Main Results:
- 1973 pathways (ADABF) and 840 pathways (ORA) were enriched for at least one exposure.
- 1227 genes within enriched pathways were identified, with 241 having strong prior evidence in OTP.
- 50% of genes mapped to cancer hallmarks, particularly Sustaining Proliferative Signalling.
Conclusions:
- The analysis provides a foundation for further functional research into CRC etiology.
- Findings may elucidate etiological associations between risk factors and CRC.
- Results could inform personalized prevention strategies for colorectal cancer.
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