Prospective study of DNA methylation at LINE‐1 and Alu in peripheral blood and the risk of prostate cancer. Issue 15 (7th August 2015)

• Record Type: Journal Article
• Authors: Barry, Kathryn Hughes; Moore, Lee E.; Liao, Linda M.; Huang, Wen‐Yi; Andreotti, Gabriella; Poulin, Matthew; Berndt, Sonja I.
• Is Part Of: Prostate. Volume 75:Issue 15(2015)
• Page Start: 1718
• Page End: 1725
• Publication Date: 2015-08-07
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.23053
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pros23053-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Evidence suggests that global blood DNA methylation levels may be associated with the risk of various cancers, but no studies have evaluated this relationship for prostate cancer.</p> </sec> <sec id="pros23053-sec-0002" sec-type="section"> <title>METHODS</title> <p>We used pyrosequencing to quantify DNA methylation levels at the long interspersed nuclear element 1 (<italic>LINE‐1</italic>) and <italic>Alu</italic> repetitive elements in pre‐diagnostic blood samples from 694 prostate cancer cases and 703 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We evaluated prostate cancer risk associated with the mean methylation level for each element using logistic regression, adjusting for potential confounders.</p> </sec> <sec id="pros23053-sec-0003" sec-type="section"> <title>RESULTS</title> <p>We did not observe a significant association with prostate cancer for <italic>LINE‐1</italic> [odds ratio (OR) for the highest compared to the lowest quartile = 1.01, 95% confidence interval (CI): 0.73–1.39, <italic>P</italic><sub>trend</sub> = 0.99] or <italic>Alu</italic> (OR = 0.94, 95% CI: 0.68–1.29, <italic>P</italic><sub>trend</sub> = 0.69) methylation levels overall. However, for <italic>Alu</italic>, we observed that higher DNA methylation levels were associated with a significant increased risk for those diagnosed 4 or more years after blood draw (OR = 2.26, 95% CI: 1.27–4.00, <italic>P</italic><sub>trend</sub> = 4.4 × 10<sup>−3</sup>). In contrast, there was no association for those diagnosed 2 (OR = 1.13, 95% CI: 0.67–1.90, <italic>P</italic><sub>trend</sub> = 0.64) or 3 years after draw (OR = 1.22, 95% CI: 0.71–2.07, <italic>P</italic><sub>trend</sub> = 0.32), and a decreased risk for those diagnosed less than 2 years after draw (OR = 0.40, 95% CI: 0.25–0.65, <italic>P</italic><sub>trend</sub> = 3.8 × 10<sup>−5</sup>; <italic>P</italic><sub>heterogeneity</sub> = 5.3 × 10<sup>−6</sup>).</p> </sec> <sec id="pros23053-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Although <italic>LINE‐1</italic> DNA methylation levels were not associated with prostate cancer, we observed an association for <italic>Alu</italic> that varied by time from blood draw to diagnosis. Our study suggests that elevated <italic>Alu</italic> blood DNA methylation levels several years before diagnosis may be associated with an increased prostate cancer risk. <italic>Prostate 75:1718–1725, 2015</italic>. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>