Pooling Resources to Examine Associations Between Vitamin D and Risk of Rarer Cancers
Division Of Cancer Epidemiology And GeneticsQuestions about whether vitamin D can increase or reduce the risks of certain cancer types remain vigorously debated in the scientific community. For researchers studying the effect of vitamin D on rarer types of cancer –such as pancreatic and ovarian cancer – the difficulty of teasing out the effects of the vitamin in epidemiologic studies are compounded by the relative scarcity of patients to study.
In 2007, Demetrius Albanes, M.D., senior investigator in the Nutritional Epidemiology Branch of NCI’s Division of Cancer Epidemiology and Genetics, joined with a group of scientists from the United States and abroad to launch the NCI Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. The project* was designed to gather data on enough patients with less common cancers to allow the researchers to more accurately estimate the associations between serum vitamin D concentrations and the development of six malignancies: pancreatic, ovarian, upper gastrointestinal (including esophagus and stomach), endometrial, renal, and non-Hodgkin lymphoma.
The project has studied over 5,000 patients diagnosed with one of these rarer cancers and over 5,000 matched control participants without cancer, taken from 10 participating cohort studies. In order to remove the variability sometimes found when blood samples are analyzed in different laboratories and at different times, samples from cancer cases and control participants from all 10 cohorts were analyzed in the same dedicated laboratory with the same equipment over a 3-month period.
In addition, “we matched the cases and controls for the calendar date of when their blood was collected and therefore for the season and approximate sun exposure at the time of collection,” explained Dr. Albanes. “We also adjusted for season of collection in our statistical models.” This is important, because blood levels of vitamin D are influenced by sun exposure and can vary drastically between seasons and by level of outdoor activity, making the date of blood collection an important factor to control for in such studies.
According to published results** and contrary to the researchers’ expectations, “we did not see lower cancer risk in persons with high vitamin D blood concentrations compared to normal concentrations for any of these cancers, nor did we see higher cancer risk for participants with low levels,” reported Dr. Albanes.
The researchers did observe an increased risk of pancreatic cancer in patients with the highest blood levels of vitamin D, a finding seen previously by some studies. “This result is a bit troubling, since people tend to believe that taking more vitamin D can only be beneficial,” noted Dr. Albanes. “So this needs to be clarified, and it’s one thing that we’re going to follow up on in future studies.”
The Vitamin D Pooling Project has also examined blood samples from their cohorts’ patients at the genetic level. In another published report***, the researchers described findings from a genome-wide association study to discover common variations in several genes that are associated with circulating vitamin D levels. One of the genes identified, codes for a binding protein that transports vitamin D within the body and three other genes code for proteins that are involved in vitamin D synthesis and metabolism.
The next step for the investigators will be to look at whether these genetic variations mediate the relationship between circulating vitamin D and cancer risk. “Knowing people’s genetic predisposition to higher or lower vitamin D levels should help us refine the relationship between people’s actual vitamin D exposures and cancer risk,” Dr. Albanes explained. “Some of the inconsistencies we’ve seen across vitamin D studies to date may be due to such genetic variations.”
* Project Number: Z01 CP010195-04
** Helzlsouer KJ for the VDPP Steering Committee. Overview of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. American Journal of Epidemiology, 2010;172(1):4–9.
***Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, Jacobs EJ, Ascherio A, Helzlsouer K, Jacobs KB, Li Q, Weinstein SJ, Purdue M, Virtamo J, Horst R, Wheeler W, Chanock S, Hunter DJ, Hayes RB, Kraft P, Albanes D. Genome-wide association study of circulating vitamin D levels. Human Molecular Genetics, 2010;19(13):2739-45.