Abstract:
Background: Colorectal carcinoma (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. Emerging evidence suggests that vitamin D, beyond its classical role in bone metabolism, may influence carcinogenesis through its effects on cell proliferation, differentiation, apoptosis, and immune modulation. However, the relationship between vitamin D and CRC remains inconsistent across studies. This systematic review aims to comprehensively evaluate the evolving role of vitamin D in colorectal cancer, including its impact on incidence, disease progression, and survival outcomes.
Methodology: This systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 36 studies were initially identified through systematic screening, of which 32 studies met the inclusion criteria after excluding four ineligible studies. The included studies comprised observational studies (cohort and case-control) as well as randomized controlled trials. A descriptive assessment of study quality and risk of bias was performed using validated tools, including the Newcastle-Ottawa Scale (NOS) and Cochrane Risk of Bias tool, where applicable. No studies were excluded solely based on quality assessment; however, methodological limitations were considered during interpretation. Due to substantial heterogeneity in study design, vitamin D assessment (serum levels vs. dietary intake), supplementation protocols, and reported outcomes, a quantitative meta-analysis was not feasible. Therefore, a narrative synthesis approach was employed. Risk of bias was evaluated across domains including selection bias, confounding, exposure measurement, outcome assessment, and reporting bias, with independent reviewer assessment to ensure objectivity.
Results: The majority of included studies demonstrated an inverse association between circulating vitamin D levels and colorectal cancer risk, with higher serum 25-hydroxyvitamin D concentrations consistently associated with reduced incidence of CRC. Several studies also reported a protective role of vitamin D in early carcinogenesis, including reduced adenoma formation. Evidence regarding disease progression indicated that adequate vitamin D levels were associated with decreased tumor proliferation, improved differentiation, and reduced metastatic potential. Survival outcomes were generally favorable in patients with higher baseline vitamin D levels, with multiple studies reporting improved overall survival and reduced mortality. However, findings from interventional studies on vitamin D supplementation were heterogeneous, with some demonstrating survival benefits while others showed no significant effect on CRC incidence. Variability in study design, dosing regimens, baseline vitamin D status, and follow-up duration contributed to observed inconsistencies.
Conclusion: This systematic review supports a potential protective and prognostic role of vitamin D in colorectal carcinoma. While observational evidence consistently indicates beneficial associations, further high-quality randomized controlled trials are required to establish causality and define optimal supplementation strategies.
