Association of DNA damage repair related genes with prostate cancer: A multi-omics Mendelian Randomization analysis

The relationship between prostate cancer and DNA damage repair remains incompletely elucidated. This study employs Mendelian Randomization to explore the causal relationships between DNA Damage Repair-related gene methylation, expression, and protein abundance and prostate cancer risk. A comprehensive analysis was conducted on 2736 DNA Damage Repair-related genes identified from the GeneCards database using Summary-data-based Mendelian Randomization. The study utilized quantitative trait loci datasets from multiple European cohorts, alongside Genome-Wide Association Studies data. Candidate gene expression patterns in prostate cancer tissue were further examined using the Human Protein Atlas and Tumor Immune Single-cell Hub 2 databases. Summary-data-based Mendelian Randomization analysis identified significant associations of genetically predicted RPA2 and POLI with prostate cancer risk. Immunohistochemical analyses from the human protein atlas database confirmed RPA2 and POLI expression in prostate cancer tissue, while single-cell sequencing data from the tumor immune single-cell hub 2 database indicated differential expression across distinct cellular subpopulations. Our study reveals a genetically inferred causal role for DDR-related genes RPA2 and POLI in prostate cancer risk. These findings may enhance the understanding of the molecular mechanisms linking DNA Damage Repair-related genes and prostate cancer.