Vitamin D deficiency linked to higher cancer mortality

By Vijay Kumar MalesuReviewed by Benedette Cuffari, M.Sc.Aug 20 2024

In a recent study published in Nutrients, researchers review how vitamin D deficiency affects the risk of cancer-related mortality.

Study: Umbrella Review on the Relationship between Vitamin D Levels and Cancer. Image Credit: Tatyana Soares / Shutterstock.com

Vitamin D and cancer

Between 2007 and 2017, a 25% increase in global cancer mortality was reported. By 2019, cancer caused over 30% of deaths in western Europe, thus making it the second leading cause of death.

Rising cancer rates have been primarily attributed to the aging population. Age-related vitamin D deficiency has been linked to increased cancer incidence and mortality.

Previous studies have shown that higher 25 hydroxyvitamin (OH)D levels following ultraviolet radiation (UV-B) exposure may offer protective effects against cancer. Nevertheless, further research is needed to clarify the causal relationship between vitamin D levels and cancer outcomes, as well as address the methodological limitations of existing studies.

About the study

Following a registered protocol International Prospective Register of Systematic Reviews (PROSPERO), the current study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist with modifications for its umbrella design.

The researchers utilized an approach based on a prior umbrella review using the Population, Intervention, Comparison, Outcome, Study design (PICOS) framework to structure the search strategy, focusing on populations at risk or diagnosed with specific cancers. Systematic reviews, with or without meta-analyses, were included in the current study if they included at least two randomized controlled trials (RCTs) or cohort studies and were published in English or German between 2010 and 2020.

Searches were conducted in PubMed and the Cochrane Library. Relevant reviews were organized using Citavi, whereas data were extracted into tables detailing study characteristics and outcomes for each cancer type.

The quality of the included reviews was assessed with the A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2 tool, which is appropriate for reviews containing both RCTs and observational studies. Reviews were rated based on the presence of critical and non-critical weaknesses, with evidence levels classified according to the Oxford Center for Evidence-Based Medicine.

Study findings 

The literature search led to the identification of 182 articles from PubMed, 57 from the reference lists of relevant reviews, and three from the Cochrane Library. These articles covered various cancers, 90, 52, 69, 18, and 17 of which were focused on breast, prostate, colorectal, pancreatic, and lung cancers, respectively.

After screening titles, abstracts, and full texts, 41 reviews were included in the qualitative synthesis. Thirty-four of these studies provided data on 25(OH)D levels and cancer, whereas seven studies examined the potential anti-cancer effects of vitamin D intake.

For breast cancer, thirteen reviews were analyzed, ten of which included meta-analyses. Most reviews identified significant inverse associations between higher 25(OH)D levels and lower breast cancer incidence and mortality, suggesting a protective effect. However, these findings are based on observational studies, thus limiting the ability to infer causality.

In prostate cancer, nine reviews were examined with mixed results. Although some studies indicated a higher risk of prostate cancer with elevated 25(OH)D levels, others did not identify a significant association. Higher 25(OH)D levels appeared to be protective against prostate cancer-related mortality; however, the evidence was primarily obtained from observational studies.

Pancreatic cancer results were less conclusive, with two reviews showing no significant association between 25(OH)D levels and cancer incidence. However, one study reported a significant inverse relationship between 25(OH)D levels and pancreatic cancer mortality, thus suggesting a potential protective effect.

For colorectal cancer, twelve reviews were included, most of which identified significant inverse associations between higher 25(OH)D levels and reduced incidence and mortality, thereby supporting a protective role. Nevertheless, the evidence remains limited to observational data.

Lung cancer results were inconsistent, with some reviews indicating a protective effect of higher 25(OH)D levels, whereas others did not identify a significant association. Mortality data were similarly mixed, with few studies reporting inverse associations between 25(OH)D levels and lung cancer mortality.

The methodological quality of the included reviews varied. None of the studies were rated as high quality, five were considered to be of moderate quality, and five were of low quality. Most of the studies were considered to be of ‘critically low quality’ due to limitations in critical domains of the AMSTAR 2 tool. 

Conclusions

Th current review identified consistent inverse correlations between 25(OH)D levels and cancer incidence, except for prostate cancer. Stronger inverse correlations were observed with mortality across all cancers.

However, most of the reviewed studies were observational, thus limiting causal inferences and raising concerns about reverse causation. Variations in 25(OH)D categorization and methodological differences between studies also complicate quantifying these relationships.