Inactive

BACKGROUND Pancreatic adenocarcinoma (PDA) is among the most fatal cancers worldwide and one for which there are few established preventable risk factors beyond cigarette smoking, diabetes, and overwe... BACKGROUND Pancreatic adenocarcinoma (PDA) is among the most fatal cancers worldwide and one for which there are few established preventable risk factors beyond cigarette smoking, diabetes, and overweight and obesity. The effect of other exposures is unclear mostly due to inconsistent findings. The lack of identification of consistent risk factors likely reflects the methodological difficulties including reverse causation as well as selection, survival, recall and surrogate reporting biases associated with collecting data for this rapidly fatal gastrointestinal cancer. Prospective studies do not have these problems. Few studies have evaluated trace elements and risk of pancreatic cancer in non-occupational cohorts. Limitations of these studies were the small number of pancreatic cancer cases and/or the cases were from retrospective studies that may have issues with reverse causation. The Metabolic Epidemiology Branch (MEB), Division of Cancer Epidemiology and Genetics (DCEG), of the National Cancer Institute (NCI) is conducting a study to determine whether trace elements are associated with pancreatic cancer. Elements shall be measured prospectively in blood samples (either whole blood or red blood cell (RBC) samples) from pancreatic cancer cases and non-cases. OBJECTIVE The MEB plans to measure blood concentrations of trace (i.e. Cu, Zn, Fe, Mg) and ultra-trace (i.e. Cd, Cr, Pb, As, Hg) elements measured in prediagnostic blood samples (whole blood or RBCs) using inductively coupled plasma mass spectrometry (ICP-MS) in a nested case-control study of pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Trial cohort. The aim of this study is to determine whether blood concentrations of trace (i.e. Cu, Zn, Fe, Mg) and ultra-trace (i.e. Cd, Cr, Pb, As, Hg) elements are associated prospectively with pancreatic cancer. SCOPE Utilizing a nested case-control design within the Prostate, Lung, Colorectal, and Ovarian Cancer Trial cohort, this project shall examine the association between blood concentrations of trace (i.e. Cu, Zn, Fe, Mg) and ultra-trace (i.e. Cd, Cr, Pb, As, Hg) elements and risk of pancreatic cancer. The elements shall be measured on incident pancreatic cancer cases and controls (84 cases, 168 controls, 25 blinded QC samples, total 277 samples) using inductively coupled plasma mass spectrometry (ICP-MS). TASKS The Contractor shall: 1. Store samples immediately after shipment is received from the NCI in -80 degrees until ready for assays. The NCI will ship the samples to the Contractor within 30 days from the effective start date of award; 2. Measure blood concentrations of trace (i.e. Cu, Zn, Fe, Mg) and ultra-trace (i.e. Cd, Cr, Pb, As, Hg) elements using whole blood or RBCs. The sample volume required is 350 µL. Three subsamples shall be prepared from the original volume for the analysis as follows: The first subsample of 300 µL shall be diluted 1:10 with 2% HNO3 and 1% butanol. This sample shall be analyzed for Cr, Cd, Pb, As, and Co using a Perkin Elmer 300X inductively coupled plasma mass spectrometer (ICP-MS) in kinetic energy discrimination (KED) with He flow rates up to 6.25 L/min; The second subsample of 25 µL shall be diluted 1:300 with 2% HNO3 and analyzed for Fe, Cu, Zn, Mg, and Ca using ICP-MS with KED with He flow rates up to 4 L/min; and The third subsample of 25 µL shall be analyzed using a Nippon MA-3000 direct thermal combustion mercury analyzer (DMA). The samples shall be analyzed in batches of 90 samples for the ICP-MS analysis and 30 samples for the DMA analysis. Each sample batch shall include analytical method blanks, Seronorm™ and National Institute of Standards and Technology (NIST) quality control materials; 3. The boxed samples shall be sent in batches of 30 to accommodate both the 30 sample and 90 sample batch sizes above. All batches and samples within the batches shall be assayed in the order provided by the NCI. All samples shall be sent at the same time. All analytical work performed by the Contractor shall be conducted under conditions of careful quality control and shall follow the laboratory’s quality control procedures. All Contractor internal quality control charts shall be provided to the NCI after the first batch and at completion of the work. The NCI shall review the data for the blinded quality control samples to assure that satisfactory reproducibility is being provided. 4. The Contractor shall notify the NCI TPC immediately via e-mail or phone call if any unusual problems develop over the course of the project and/or explanations for repeating analyses, such as failure of analytical and quality control procedures, breakdown of freezers, instrumentation and equipment, and major changes in personnel that would produce delays or that would adversely influence the quality of the laboratory performance. 5. After the assays are run on each batch, residual samples shall be stored in the laboratory at -80 degrees Centigrade. All biological materials provided by the U.S. Government, all residual specimens, and all data generated shall be the property of the U.S. Government and shall be returned to the U.S. Government repository via FedEx after the assays are completed and data approved by NCI TPC.