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Colon cancer is one of the deadliest types of cancer in the United States, with close to 50,000 projected deaths in 2024. The disease requires early diagnosis to optimize chances of survival by enabling timely administration of treatment. To investigate the key non-genetic (NG) factors influencing the onset of colon cancer and evaluate how genetic factors enhance the performance of machine learning (ML) models in predicting incidence, we incorporated polygenic risk scores (PRSs) alongside NG data in ML models to predict 10-year incident risk prediction of colon cancer using data from the UK Biobank. This approach enabled us to assess the added predictive value of PRSs in multi-modal models in estimating the 10-year risk of developing colon cancer over NG data alone. Moreover, our research focused on identifying the most relevant and predictive PRS and validating them using a robust ML framework. To ensure the robustness, we restricted the cohort to White British individuals to minimize ancestry-related heterogeneity. PRSs have proven effective in enhancing disease prediction for conditions such as breast cancer, myocardial infarction, and schizophrenia, reinforcing their relevance in clinical research. Exploring six PRSs, our goal was to minimize false negatives while simultaneously maximizing area under the receiver-operating characteristic curve (AUC), in order to improve early detection rates by identifying those who are at risk for colon cancer. This research shows that PRSs can be used to enhance overall predictive ability of ML models in colon cancer research over NG factors alone, bolstering the argument for incorporating PRSs into routine clinical practice. PRSs can also help minimize false negatives, a key feature for disease prediction models, as missed potential diagnoses are life-threatening.