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Sufficient plasma vitamin D levels linked to improved pancreatic cancer survival
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Plasma 25-hydroxyvitamin D levels of 30 ng/mL or higher appeared associated with longer pancreatic cancer survival, according to an analysis of five U.S. prospective cohort studies.
“Pancreatic cancer is the third-leading cause of cancer-related deaths in the United States, and most patients die within 12 months of diagnosis,” Brian M. Wolpin, MD, MPH, co-director of Pancreas and Biliary Tumor Center and physician at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School, and colleagues wrote. “Recent studies in laboratory models of pancreatic cancer have demonstrated the therapeutic potential of vitamin D analogs by engagement of vitamin D receptor in tumor cells and supportive cells within the tumor stroma.”
Brian M. Wolpin
However, few studies have been conducted to evaluate the association of vitamin D levels with pancreatic cancer survival.
Wolpin and colleagues evaluated the association between plasma 25-hydroxyvitamin D [25(OH)D] levels and survival using data from 493 patients enrolled in five prospective United States cohorts. Patients were diagnosed with pancreatic adenocarcinoma from 1984 to 2008, had available plasma data and had no prior history of cancer (except melanoma skin cancer).
The median time between blood draw and pancreatic cancer diagnosis was 6.7 years.
The mean 25(OH)D level prior to diagnosis was 24.6 ng/mL, and 165 (33%) patients were considered vitamin D insufficient.
Researchers categorized patients into three groups based on prediagnostic 25(OH)D levels:
- less than 20 ng/mL, or insufficient levels (n = 165; median age at blood draw, 63.9 years, median age at diagnosis, 71.1 years);
- 20 ng/mL to 30 ng/mL, or relative insufficiency (n = 212; median age at blood draw, 64 years; median age at diagnosis, 71.7 years); and
- 30 ng/ml and higher, or sufficient levels (n = 116; median age at blood draw, 61.6 years; median age at diagnosis, 70.2 years).
By the end of follow-up, 464 (94%) patients had died.
In analyses adjusted for diagnosis year, disease stage and blood collection month, patients with relative 25(OH)D insufficiency (HR = 0.79; 95% CI, 0.48-1.29) and within the sufficient group (HR = 0.66; 95% CI, 0.49-0.9) had a decreased risk for death compared with patients in the insufficient group.
Patients in the sufficient group whose blood was collected within 5 years of diagnosis had the strongest association between prediagnostic 25(OH)D levels and improved survival (HR = 0.58; 95% CI, 0.35-0.98).
Researchers then evaluated whether 30 tagging single nucleotide polymorphisms in the vitamin D receptor gene correlated with survival, where P < .002 would indicate statistical significance.
Results showed rs7299460 most strongly correlated with survival (HR per minor allele = 0.8; 95% CI, 0.68-0.95); however, no SNP at the vitamin D receptor gene met the significance threshold.
Wolpin and colleagues acknowledged that therapy varies for pancreatic cancer, but they could not control for these differences because that information was not collected. Still, researchers noted that chemotherapy and radiation have had only modest impacts on survival.
“When considering these findings together with previously reported preclinical data in pancreatic cancer models, agonists of the vitamin D receptor are a potentially attractive therapeutic approach for investigation in this highly lethal malignancy,” Wolpin and colleagues wrote. “Whether addition of vitamin D analogs to systemic chemotherapy can further improve patient outcomes is currently being investigated.” – by Nick Andrews
Disclos ure: Wolpin reports a consultant/advisory role with Genentech. Please see the full study for a list of all other researchers' relevant financial disclosures.
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