Genetic Marker in the Vitamin D Receptor Gene Associated With Increased Overall Survival for Pancreatic Cancer Patients

By Jeremy Moore

LAKE TAHOE, Nev. — Pancreatic cancer patients with a genetic marker linked to increased expression of the receptor for vitamin D have higher rates of overall survival, according to findings presented at the American Association for Cancer Research’s Pancreatic Cancer: Progress and Challenges conference, held here June 18-21.

“Based on these findings, we should refocus our attention on the role of the vitamin D pathway in pancreatic cancer because it may have an impact on the survival of patients,” said Federico Innocenti, MD, PhD, associate professor of pharmacy at the UNC Eshelman School of Pharmacy. Dr. Innocenti is a member of UNC Lineberger.

In a previous study, Innocenti and his colleagues prospectively collected DNA from 365 patients enrolled in the CALGB 80303 randomized phase III clinical trial testing two treatments for advanced pancreatic cancer. A genome-wide association study (GWAS) was conducted using these DNA samples to identify genetic variations known as single-nucleotide polymorphisms (SNPs) associated with better or worse patient outcome. In the new study, the 300 SNPs previously shown to be most strongly associated with overall survival were tested for their association with overall survival in 408 patients of European descent with advanced pancreatic cancer treated at the Mayo Clinic.

Among the SNPs with concordant effects on overall survival of patients in the CALGB 80303 clinical trial and treated at the Mayo Clinic was a SNP in the gene coding for the vitamin D receptor. This SNP, known as rs2853564 in the VDR gene, was associated with better overall survival.

Patients with two copies of rs2853564 in VDR had a median overall survival of 10.5 months in the Mayo Clinic group and 8.9 months in the CALGB 80303 study. Patients with one copy had a median overall survival of 8.34 months in the Mayo Clinic group and 5.9 months in the CALGB 80303 study. Patients with no copies of the variant allele had a median overall survival of 6.6 months in the Mayo Clinic group and 4.7 months in the CALGB 80303 study.  While Innocenti does not see this study having any immediate clinical implications, he believes it provides more information about the link between vitamin D biology and pancreatic cancer.

Funding for the research was provided by the National Cancer Institute, the National Institutes of Health and UNC.

Howard McLeod, PharmD, Fred Eshelman Distinguished Professor of Pharmacogenomics and Individualized Therapy at the UNC Eshelman School of Pharmacy and the director of the UNC Institute for Pharmacogenomics and Individualized Therapy, was a co-author of the finding. Dr. McLeod is a UNC Lineberger faculty member.

Other authors are from the University of California at San Francisco, San Francisco, California; RIKEN, Yokohama, Japan; the University of Chicago, Chicago, Illinois; Mayo Clinic, Rochester, Minnesota; and Duke University Medical Center, Durham, NC.

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