Background: The NIH All of Us research program is a prospective, nationwide cohort study currently enrolling more than 594,000 people in the United States. Chronic diseases such as hypertension (HTN), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HLD) are associated with increased morbidity and mortality in cancer patients. Few studies have assessed the impact of each illness on colon cancer patients using extensive population data in the United States. In this study, we investigate the prevalence of these disorders in colon cancer patients and how they affect physical health and quality of life using the All of Us research database. Methods: In this cross-sectional study, we included participants from All of Us dataset version 6, which includes data collected between May 6, 2018, and January 1, 2022, who had available electronic health records (EHR) data. We identified individuals with colon cancer using the ICD-9/ICD-10 diagnosis code and then examined the presence of three disease conditions from the EHR data. Each disease's prevalence and odds ratio were calculated among colon cancer patients (N = 2,366) compared to all participants with available EHR data (N = 258,188). Responses to two questions (perception of overall physical health and quality of life) were studied with options scored from 1 (Poor) to 5 (Excellent). We compared the mean scores between colon cancer patients and colon cancer patients with HLD (N = 1,254), T2DM (N = 356), and HTN (N = 1,234). The odds ratio was calculated using unconditional maximum likelihood estimation. The study compared scores using the Wilcoxon rank sum test, with a significance level of P < 0.05. Analysis was performed in the web-based platform Jupyter Notebook using the programming language R. Results: The prevalence of HTN, HLD, and T2DM in participants with colon cancer was 52.3%, 53.0%, and 15.1%, respectively, compared to 21.6%, 22%, and 7.9% in all participants. The calculated odds ratio of HTN, HLD, and T2DM in participants with colon cancer was 4.05 (95% confidence interval: 3.74-4.40), 4.06 (3.74-4.41), and 2.08 (1.86-2.33), respectively. Mean scores of physical health and quality of life were significantly lower in colon cancer with T2DM patients compared to colon cancer patients. However, the scores of participants with colon cancer and HLD or colon cancer and HTN were not significantly different from participants with colon cancer. Conclusions: Our analysis shows that individuals with colon cancer have a higher prevalence of HTN, T2DM, and HLD than all participants in the All of Us database. T2DM in colon cancer patients is associated with poor self-reported physical health and quality of life. This highlights the importance of regular screening and optimal control and management of chronic disorders in patients with colon cancer.