Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer |
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| Institution: | 1. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia;2. University of Queensland, Brisbane, Queensland, Australia;3. Curtin University, Perth, Western Australia, Australia;4. Yale School of Public Health, New Haven, CT, United States;5. Department of Pathology, The University of Melbourne, Carlton, 3010 Victoria, Australia;6. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, Victoria 3010, Australia;1. Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland OH, USA;2. Department of Surgery, University of Michigan, Ann Arbor, MI, USA;1. International Diabetes Federation, Brussels, Belgium;1. Medicinal Chemistry, School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK;2. Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA;1. Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, United States;2. Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, United States |
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| Abstract: | Pancreatic cancer is a leading cause of cancer-related deaths worldwide. Methylation of DNA may influence risk or be a marker of early disease. The aim of this study was to measure the association between methylation of three DNA repetitive elements in white blood cell (WBC) DNA and pancreatic cancer.DNA from WBCs of pancreatic cancer cases (n = 559) and healthy unrelated controls (n = 603) were tested for methylation of the LINE-1, Alu and Sat2 DNA repetitive elements using MethyLight quantitative PCR assays. Odds ratios (ORs) and 95% confidence intervals (95%CI) between both continuous measures of percent of methylated sample compared to a reference (PMR) or quintiles of PMR and pancreatic cancer, adjusted for age, sex, smoking, BMI, alcohol and higher education, were estimated.The PMR for each of the three markers was higher in cases than in controls, although only LINE-1 was significantly associated with pancreatic cancer (OR per log unit = 1.37, 95%CI = 1.16–1.63). The marker methylation score for all three markers combined was significantly associated with pancreatic cancer (p-trend = 0.0006). There were no associations between measures of PMR and either presence of metastases, or timing of blood collection in relation to diagnosis, surgery, chemotherapy or death (all p > 0.1).We observed an association between methylation of LINE-1 in WBC DNA and risk of pancreatic cancer. Further studies are needed to confirm this association. |
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| Keywords: | Pancreatic cancer White blood cell DNA DNA methylation Repetitive DNA elements LINE-1 Alu Sat2 |
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