Interplay between Genome, Metabolome and Microbiome in Colorectal Cancer

Area of Science:

• Genomics and Multi-omics Research
• Cancer Biology and Etiology
• Personalized Medicine and Risk Prediction

Background:

• Colorectal cancer (CRC) development is influenced by environmental, genetic, and microbial factors.
• While the roles of the microbiome and metabolome in CRC are studied, their interplay with host genetics is not well understood.
• Clarifying these multi-omic interactions is crucial for advancing CRC research and prevention strategies.

Purpose of the Study:

• To investigate the interplay between host genetics, microbiome, and metabolome in colorectal cancer (CRC) and adenoma risk.
• To identify specific genetic variants and metabolic factors associated with CRC and adenoma development.
• To develop integrated multi-omic risk prediction models for colorectal cancer.

Main Methods:

• Sequencing of 120 individuals to analyze associations between genetic variants, microbiome, and metabolome components.
• Epistasis analysis of genes within cholesterol pathways and Mendelian randomization for modifiable risk factors.
• Integration of three omic layers (genetics, microbiome, metabolome) to build predictive models.

Main Results:

• Identified genetic variants (e.g., in LINC001605, PROKR2, CCSER1) associated with metabolome/microbiome components and CRC/adenoma risk.
• Found significant gene-gene interactions in cholesterol metabolism, with HDL cholesterol levels impacting adenoma and CRC risk.
• Integrated multi-omic models achieved high area under the curve (AUC) values (>0.91) for risk prediction.

Conclusions:

• The integration of genetic, microbial, and metabolic data provides novel insights into the biological mechanisms underlying adenoma and CRC development.
• Each omic layer offers complementary information, enhancing the accuracy and comprehensiveness of colorectal cancer risk prediction models.
• This multi-omic approach holds promise for improving early detection and personalized prevention strategies for colorectal cancer.