Alterations in DNA methylation patterns, both at specific loci and overall in the genome, have been associated with many different health outcomes. In cancer and other diseases, most of these changes have been observed at the tissue level. Data on whether DNA methylation changes in white blood cells (WBC) can serve as a useful biomarker for different health outcomes are much more limited, but rapidly emerging. Epidemiologic studies have reported associations between global WBC methylation and several different cancers including cancers of the colon, bladder, stomach, breast and head and neck, as well as schizophrenia and myelodysplastic syndrome. Evidence for WBC methylation at specific loci and disease risk is more limited, but increasing. Differences in WBC DNA methylation by selected risk factors including demographic (age, gender, race), environmental exposures (benzene, persistent organic pollutants, lead, arsenic, and air pollution), and other risk factors (cigarette smoke, alcohol drinking, body si...

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DNA methylation measured in white blood cell DNA is increasingly being used as in studies of cancer susceptibility. However, little is known about the correlation between different assays to measur...

Background: Lower levels of global DNA methylation in tissue and blood have been associated with increased cancer risk. Conversely, cross-sectional an

Background Exposure to a pre-natal famine environment has been associated with a persistent decrease in DNA methylation of the IGF2 gene, although study findings on other loci have been highly variable. There have been no studies to date of the relation between pre-natal famine and overall global DNA methylation in adulthood. Methods Our study population includes 350 births with pre-natal exposure to the Dutch famine of 1944–45 selected from three birth clinics, 290 births from these clinics born before or after the famine as unexposed time controls and 307 same-sex siblings of either birth group as unexposed family controls. All study subjects were interviewed and underwent a medical examination at a mean age of 58 years when blood samples were also collected. As measures of genomic DNA methylation, we analysed two repetitive elements, LINE-1 (long interspersed nucleotide element 1) and Sat2 (Satellite 2 DNA sequence) by pyrosequencing and MethyLight, respectively, and overall genomic DNA methylation using the Luminometric methylation assay (LUMA). Results Mean DNA methylation by LUMA was 75.2% [standard deviation (SD) 4.7], by LINE-1 was 77.1% (SD 2.5) and by Sat2 was 122.2 (SD 56.2). Pre-natal famine exposure was associated with negligible changes in all three assays {LUMA: −0.16% [95% confidence interval (95% CI) −0.49 to 0.81], P = 0.63; LINE-1: −0.05 % (95% CI −0.33 to 0.22), P = 0.70; and Sat2: −0.51% (95% CI −7.38 to 6.36), P = 0.88} relative to unexposed controls, adjusting for age at examination and within family clustering. Conclusion Our results show no relation between overall global DNA methylation in adults and pre-natal famine exposure. Further work should focus on selected regions in the genome that may be differentially methylated in response to changes in early life exposures and predict adult health outcomes.

Global decreases in DNA methylation, particularly in repetitive elements, have been associated with genomic instability and human cancer. Emerging, though limited, data suggest that in white blood cell (WBC) DNA levels of methylation, overall or in repetitive elements, may be associated with cancer risk. We measured methylation levels of three repetitive elements [Satellite 2 (Sat2)], long interspersed nuclear element-1 (LINE-1) and Alu) by MethyLight, and LINE-1 by pyrosequencing in a total of 282 breast cancer cases and 347 unaffected sisters from the New York site of the Breast Cancer Family Registry (BCFR) using DNA from both granulocytes and total WBC. We found that methylation levels in all markers were correlated between sisters (Spearman correlation coefficients ranged from 0.17 to 0.55). Sat2 methylation was statistically significantly associated with increased breast cancer risk [odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.09–4.03; for each unit decrease in the natural log of the methylation level, OR = 2.12, 95% CI = 0.88–5.11 for the lowest quartile compared with the highest quartile]. These associations were only observed in total WBC but not granulocyte DNA. There was no association between breast cancer and LINE-1 and Alu methylation. If replicated in larger prospective studies, these findings support that selected markers of epigenetic changes measured in WBC, such as Sat2, may be potential biomarkers of breast cancer risk.