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Background: The aim of this study is to investigate whether vitamin D, calcium, ferritin, and uric acids play a beneficial biomarker role in the prevention of colorectal cancer (CRC) risk., Methods: The case-control design was employed, including 650 CRC cases and 650 controls aged 35 to 70 years, comprising both men and women. The study encompasses sociodemographic data, clinical information, radiological diagnoses, and biochemical measurements., Results: Statistically significant differences were observed between CRC and controls in terms of age, diagnostic radiology, tomography, positron emission tomography/computed tomography (PET/CT), colonoscopy, CRC awareness, risk factors, age, genetics, exposure to chemicals, inadequate nutrition, smoking, hookah and alcohol use. Significant differences were also identified in intestinal inflammations, obesity, processed foods (P < 0.001), abdominal pain and cramps, diarrhea, constipation, blood in stool, bloating (gas), irritable bowel, nausea/vomiting, anemia, stress, fatigue, weakness, and weight loss. Regarding biochemical parameters, statistically significant differences were found between CRC and controls in terms of hemoglobin, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), vitamin D, neutrophil level, red blood cell (RBC), white blood cell (WBC), platelet level, platelet count, hematocrit, potassium, sodium (Na), calcium, creatinine, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), bilirubin, uric acid, iron (Fe), ferritin, C-reactive protein (CRP), total protein, systolic blood pressure (SBP), and diastolic blood pressure (DBP) parameters (P < 0.001). Multivariate stepwise regression analysis was performed to find the best risk factors for the diagnosis of CRC as the dependent variable. As a result of the analysis, intestinal inflammation (P < 0.001), nausea/vomiting (P < 0.001), stomach pain (P = 0.003), hookah-smoking (P = 0.034), uric acid (P < 0.001), bilirubin (P < 0.001), cigarette smoke exposure (P = 0.033), processed food consumption (P = 0.002), calcium levels (P = 0.029), vitamin D deficiency (P < 0.001), and ferritin (P < 0.001) levels were identified as significant determinants for CRC., Conclusions: The current study demonstrated that vitamin D, calcium, ferritin, and uric acids play a beneficial biomarker role in reducing the risk of CRC prevention. The increase in CRC rates may be associated with lifestyle, environmental and hereditary factors, nutrition, alcohol consumption, hookah use, and cigarette smoking., Competing Interests: The author(s) declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article., (Copyright 2024, Bener et al.)