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Serum selenium and pancreatic cancer risk
Pancreatic adenocarcinoma is among the most fatal cancers worldwideand one for which few preventable risk factors is established. Selenium is an essential trace mineral that has been shown to inhibit tumorigenesis in experimental models and is associated with a reduced risk for gastrointestinal cancers in some epidemiologic studies. Selenium has not been adequately examined in association with pancreatic cancer in either experimental or epidemiologic studies. Animal studies examining the effects of selenium supplementation on pancreatic carcinogenesis show inconsistent results. One small epidemiologic study examined selenium status and pancreatic cancer and demonstrated a 4-fold increased pancreatic cancer risk for subjects with lower versus higher selenium concentrations. Several recent epidemiologic studies have reported positive associations between selenium and diabetes, a consistent risk factor for pancreatic cancer. We propose to conduct a nested case-control (200 cases, 400 matched controls) study within the PLCO Trial using T0 serum to examine whether selenium status is prospectively associated with pancreatic cancer. We hypothesize that we may observe a U shaped association between serum selenium and pancreatic cancer with both low and high concentrations of selenium being associated with increased risk of pancreatic cancer. The PLCO Trial cohort provides an opportunity to test this hypothesis in a prospective setting, avoiding the biases of retrospective research and reverse-causation. Serum selenium will be measured in the laboratory of Dr. Combs who is an international selenium expert and whose lab is able to measure selenium with high reliability using 100ul of serum. We also plan to submit a similar proposal to obtain samples from the Women's Health Initiative (WHI) to examine the selenium/pancreatic cancer association in both study populations combined to increase our study power and ability to examine interactions. This later effort is contingent upon our proposal application and approval by the WHI Steering Committee. For the purposes of this submission, our proposal should be judged alone to test for main effects but with further added value, should a study in the WHI be launched. The results from this study may provide insight into the mechanisms related to pancreatic carcinogenesis and may have important implications for the prevention of pancreatic cancer.
This proposed nested case-control study within the PLCO study cohort aims to determine whether selenium status is prospectively associated with pancreatic cancer. The primary aim of this study is: 1. To test the hypothesis that serum selenium is associated with pancreatic cancer. We hypothesize that we may observe a U shaped association between serum selenium and pancreatic cancer with both low and high concentrations of selenium being associated with increased risk of pancreatic cancer. The secondary aim of this study is: 2. To evaluate the interaction of the association between selenium status and pancreatic cancer by smoking habits, age, c-peptide concentrations and obesity.
Mitch Gail (Biostatistics Branch)
Gerald Combs (Grand Forks Human Nutrition Research Center USDA)
Richard Hayes (Occupational Epidemiology Branch)
Rachael Stolzenberg-Solomon (NCI, DCEG)