Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer

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 cance...

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Main Authors: Neale, R., Clark, P., Fawcett, J., Fritschi, Lin, Nagler, B., Risch, H., Walters, R., Crawford, W., Webb, P., Whiteman, D., Buchanan, D.
Format: Journal Article
Published: Elsevier Inc. 2014
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Online Access:http://hdl.handle.net/20.500.11937/42957
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author Neale, R.
Clark, P.
Fawcett, J.
Fritschi, Lin
Nagler, B.
Risch, H.
Walters, R.
Crawford, W.
Webb, P.
Whiteman, D.
Buchanan, D.
author_facet Neale, R.
Clark, P.
Fawcett, J.
Fritschi, Lin
Nagler, B.
Risch, H.
Walters, R.
Crawford, W.
Webb, P.
Whiteman, D.
Buchanan, D.
author_sort Neale, R.
building Curtin Institutional Repository
collection Online Access
description 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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spelling curtin-20.500.11937-429572017-09-13T15:51:04Z Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer Neale, R. Clark, P. Fawcett, J. Fritschi, Lin Nagler, B. Risch, H. Walters, R. Crawford, W. Webb, P. Whiteman, D. Buchanan, D. Alu LINE-1 Repetitive DNA elements Sat2 DNA methylation White blood cell DNA Pancreatic cancer 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. 2014 Journal Article http://hdl.handle.net/20.500.11937/42957 10.1016/j.canep.2014.08.006 Elsevier Inc. restricted
spellingShingle Alu
LINE-1
Repetitive DNA elements
Sat2
DNA methylation
White blood cell DNA
Pancreatic cancer
Neale, R.
Clark, P.
Fawcett, J.
Fritschi, Lin
Nagler, B.
Risch, H.
Walters, R.
Crawford, W.
Webb, P.
Whiteman, D.
Buchanan, D.
Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer
title Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer
title_full Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer
title_fullStr Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer
title_full_unstemmed Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer
title_short Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer
title_sort association between hypermethylation of dna repetitive elements in white blood cell dna and pancreatic cancer
topic Alu
LINE-1
Repetitive DNA elements
Sat2
DNA methylation
White blood cell DNA
Pancreatic cancer
url http://hdl.handle.net/20.500.11937/42957