title: Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer.
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.
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: Rachel.neale@qimrberghofer.edu.au.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Neale
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Clark
authors.affiliation: University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fawcett
authors.affiliation: Curtin University, Perth, Western Australia, Australia.
authors.forename: Lin
authors.initials: L
authors.lastname: Fritschi
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Belinda N
authors.initials: BN
authors.lastname: Nagler
authors.affiliation: Yale School of Public Health, New Haven, CT, United States.
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Rhiannon J
authors.initials: RJ
authors.lastname: Walters
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: William J
authors.initials: WJ
authors.lastname: Crawford
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
authors.affiliation: Department of Pathology, The University of Melbourne, Carlton, 3010 Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, Victoria 3010, Australia.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012306:Risk
chemical_list: D004247:DNA
keywords: Alu; DNA methylation; LINE-1; Pancreatic cancer; Repetitive DNA elements; Sat2; White blood cell DNA