Is There a Link Between Vitamin D and Pancreatic Cancer?

Blood vitamin D (25-hydroxyvitamin) levels may contribute to pancreatic cancer development, it has been suggested.

In recent years, several research teams have also been investigating whether vitamin D measurements in the presence of pancreatic cancer might serve as a biomarker with a prognostic role (predicting the course of the disease), in an effort to clarify this relationship.

For example, the randomized phase 3 MPACT clinical trial, in a further analysis of patients with pancreatic cancer, found no association between vitamin D levels and overall survival.

In the MPACT study, metastatic (stage 4) pancreatic cancer patients, 861 in total, received nab-paclitaxel plus gemcitabine or, for comparison, gemcitabine alone. Vitamin D level data were available for 422 patients, who were divided into 3 groups based on vitamin D level classification:

• Sufficient (>30 ng / mL)
• Relatively insufficient (20-30 ng / mL)
• Insufficient (>20 ng /mL)

Von Hoff and colleagues from the study reported no statistically significant difference in median overall survival among the 3 groups. Median overall survival was 7.9 months for the insufficient group, 9.4 months for the relatively insufficient group, and 7.8 months for the sufficient group. In intergroup analyses as well, no difference in median overall survival was seen in relation to vitamin D levels.

Although the study concluded that there was no association between vitamin D levels and overall survival, the researchers reported that the lack of a large sample and the extent of disease were influencing these findings.

Meta-analysis of studies on vitamin D and pancreatic cancer

A meta-analysis reviewing 12 studies that evaluated the effect of vitamin D levels on pancreatic cancer and mortality also found, in survival outcomes, no statistical difference.

In particular, an elevated 25 vitamin D level did not reduce pancreatic cancer risk, and the amount of vitamin D consumed was not associated with the risk of developing pancreas.

The relationship between vitamin D supplementation and pancreatic cancer

Daily vitamin D intake and pancreatic risk were also the focus of the International Pancreatic Cancer Case-Control Consortium in a pooled data analysis containing the results of 9 control studies. Unlike the meta-analysis findings, these pooled analysis data proved a link between higher vitamin D intake and increased pancreatic cancer risk. No significant effect was observed when the results were adjusted for smoking. The researchers noted that the association between vitamin D intake and pancreatic cancer might be related to low vitamin A intake.

However, data from “Pankreas Kanseri Hastalarda Biyobelirteçler Çalışması” (BIOPAC) showed that patients with vitamin D deficiency had higher levels of markers such as interleukin (IL)-6, YKL-40, and C-reactive protein (CRP), associated with inflammation. The BIOPAC researchers specifically evaluated the relationship between pretreatment vitamin D levels, inflammatory biomarkers, and overall survival in patients with pancreatic ductal adenocarcinoma (PDAC, the most common subtype of pancreatic cancer).

Patients were classified into 3 groups based on pretreatment vitamin D levels:

• Sufficient (>50 nmol / L)
• Insufficient (25-50 nmol / L)
• Deficient (<25 nmol / L)

Among all patients, 49% had either insufficient or deficient vitamin D levels, and those with vitamin D deficiency had the highest IL-6, YKL-40, and CRP levels regardless of their cancer stage.

For patients who underwent pancreatic cancer surgery (stages 1 and 2) and had vitamin D deficiency, median overall survival was shorter than for patients with sufficient vitamin D levels (18.3 months versus 29.7 months). Rasmussen and colleagues from the study said that no difference in overall survival was seen among patients with advanced pancreatic cancer, regardless of their vitamin D levels. Similarly, no statistically significant difference in median overall survival was seen among patients receiving gemcitabine whose vitamin D levels varied.

The optimal vitamin D level was defined as between 54 nmol / L and 80 nmol / L. The study researchers hypothesized that patients with minimal residual disease after surgery might be reasonable candidates for vitamin D supplementation to prevent cancer cell progression.

Vitamin D pathophysiology in pancreatic cancer

The underlying pathophysiology of vitamin D in pancreatic cancer is not fully understood. The pancreatic cancer tumor microenvironment (TMÇ) was characterized by hypoxia and immunosuppression leading to fibrosis. Increased inflammation in the TMÇ may promote angiogenesis (new blood vessel formation) and metastases. Vitamin D is most likely involved in many of these stages rather than in a single cellular pathway. In particular, the vitamin D receptor (VDR) may play a role in stimulating the immune response through the VDR-1, 25-hydroxyvitamin-D2 complex, which inhibits angiogenesis and promotes cell differentiation and apoptosis.

Vitamin D may also affect pancreatic endocrine function through insulin regulation.

Some study data suggested that vitamin D may be synergistic with chemotherapy by increasing cellular remodeling after treatment. At this point, the study findings also summarize why vitamin D is an interesting biomarker in the pancreatic cancer setting.

However, future studies need to continue obtaining data on vitamin D in pancreatic cancer, particularly regarding the possible synergy between vitamin D and chemotherapy. The location of future studies is also important because approximately 90% of a person's vitamin D requirements come from sunlight.