Five genes identified as prognostic markers for colorectal cancer through the integration of genome-wide association study and expression quantitative trait loci data

<b>Background:</b> Colorectal cancer (CRC) is a prominent form of cancer globally, ranking second in terms of prevalence and serving as a leading cause of cancer-related deaths, but the underlying biological interpretation remains largely unknown. <b>Methods:</b> We used the summary data-based Mendelian randomization method to integrate CRC genome-wide association studies (n_case = 7062; n_control = 195,745) and expression quantitative trait <i>loci</i> summary data in peripheral whole blood (Consortium for Architecture of Gene Expression: n = 2765; Genotype-Tissue Expression [v8]: n = 755) and colon tissue (colon-transverse: n = 406; colon-sigmoid: n = 373) and identified related genes. <b>Results:</b> Genes <i>ABTB1</i>, <i>CYP21A2</i>, <i>NLRP1</i>, <i>PHKG1</i> and <i>PIP5K1C</i> have emerged as significant prognostic markers for CRC patient survival. Functional analysis revealed their involvement in cancer cell migration and invasion mechanisms, providing valuable insights for the development of future anti-CRC drugs. <b>Conclusion:</b> We successfully identified five CRC risk genes, providing new insights and research directions for the effective mechanisms of CRC. The primary objective of our study was to detect functional genes and regulatory elements in colorectal cancer (CRC) by combining genome-wide association study summary data with expression quantitative trait <i>loci</i> data. Through the utilization of the summary data-based Mendelian randomization method, we successfully integrated CRC genome-wide association study and expression quantitative trait <i>loci</i> datasets, resulting in the identification of 135 risk genes associated with CRC. Comprehensive Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these 135 risk genes are significantly enriched in regulatory pathways crucial for cancer cell growth, metabolic processes and immune response. By combining data from colon adenocarcinoma and rectum adenocarcinoma cohorts within The Cancer Genome Atlas database, we discovered that among the 135 risk genes, <i>ABTB1</i>, <i>CYP21A2</i>, <i>NLRP1</i>, <i>PHKG1</i> and <i>PIP5K1C</i> are strongly associated with the survival outcomes of CRC patients. Notably, the <i>CYP21A2</i> gene exhibited a positive correlation with pathways involved in the proliferation and migration of CRC, underscoring its potential role as a susceptibility gene and a promising target for clinical intervention in CRC. These results provide important insights into the molecular mechanisms of CRC genomics and provide potential targets for treatment.