Prospective study of DNA methylation at LINE‐1 and Alu in peripheral blood and the risk of prostate cancer

Abstract

BACKGROUND 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. METHODS We used pyrosequencing to quantify DNA methylation levels at the long interspersed nuclear element 1 (LINE-1) and Alu 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. RESULTS We did not observe a significant association with prostate cancer for LINE-1 [Odds Ratio (OR) for the highest compared to the lowest quartile=1.01, 95% Confidence Interval (CI): 0.73-1.39, ptrend=0.99] or Alu (OR=0.94, 95% CI: 0.68-1.29, ptrend=0.69) methylation levels overall. However, for Alu, 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, ptrend=4.4×10−3). In contrast, there was no association for those diagnosed 2 (OR=1.13, 95% CI: 0.67-1.90, ptrend=0.64) or 3 years after draw (OR=1.22, 95% CI: 0.71-2.07, ptrend=0.32), and a decreased risk for those diagnosed less than 2 years after draw (OR=0.40, 95% CI: 0.25-0.65, ptrend=3.8×10−5; pheterogeneity=5.3×10−6). CONCLUSIONS While LINE-1 DNA methylation levels were not associated with prostate cancer, we observed an association for Alu that varied by time from blood draw to diagnosis. Our study suggests that elevated Alu blood DNA methylation levels several years before diagnosis may be associated with an increased prostate cancer risk.

World Trade Center (WTC) dust exposure in mice is associated with inflammation, oxidative stress and epigenetic changes in the lung

“…This is supported by early reports that in human blood cells, changes in Line-1 methylation correlate with susceptibility to the adverse effects of air pollution (Baccarelli et al, 2009; Bind et al, 2012). Line-1 methylation is thought to be a pre-diagnostic marker for renal cell carcinoma and prostate cancer (Andreotti et al, 2014; Barry et al, 2015; Karami et al, 2015). It remains to be determined if it is also an early marker of lung cancer after exposure to WTC dust.…”

A panel of DNA methylation signature from peripheral blood may predict colorectal cancer susceptibility

“…Peripheral blood is an easily accessible source of genomic DNA that can be used to estimate DNA methylation pro les and could serve as useful non-invasive and informative biomarkers for cancer risk (5). Several studies have investigated peripheral blood DNA methylation biomarkers in different cancer types including head and neck, urothelial, breast, lung, bladder, gastric cancer, prostate and ovarian cancers (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Some epidemiologic studies have assessed peripheral blood DNA methylation biomarkers in CRC.…”

A panel of DNA methylation signature from peripheral blood may predict colorectal cancer susceptibility

“…Peripheral blood is an easily accessible source of genomic DNA that can be used to estimate DNA methylation profiles and could serve as useful non-invasive and informative biomarkers for cancer risk (6). Several studies have investigated peripheral blood DNA methylation biomarkers in different cancer types including head and neck, urothelial, breast, lung, bladder, gastric cancer, prostate and ovarian cancers (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Some epidemiologic studies have assessed peripheral blood DNA methylation biomarkers in CRC.…”