Abstract
BackgroundAbnormal one-carbon metabolism may lead to general genomic (global) hypomethylation, which may predispose an individual to the development of colorectal neoplasia.MethodsWe evaluated the association between pre-diagnostic leukocyte genomic DNA methylation level and the risk of colorectal cancer in a nested case-control study of 358 colorectal cancer cases and 661 matched controls within the all-female cohort of the Nurses’ Health Study (NHS). Among control subjects, we further examined major plasma components in the one-carbon metabolism pathway in relation to genomic DNA methylation level. Liquid chromatography/tandem mass spectrometry was used to examine leukocyte genomic DNA methylation level. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression.ResultsOverall genomic DNA methylation level was not associated with the risk of colorectal cancer (p for trend, 0.45). Compared with women in the lowest quintile of methylation, the multivariate OR of colorectal cancer risk was 1.32 (95% CI, 0.82–2.13) for those in the highest quintile. We did not find significant associations between major plasma components of one-carbon metabolism or risk factors for colorectal cancer and genomic DNA methylation level (all p for trend >0.05). Also, neither one-carbon metabolism-related plasma components nor well-known risk factors for colorectal cancer modified the association between genomic DNA methylation level and the risk of colorectal cancer (all p for interaction >0.05).ConclusionsWe found no evidence that hypomethylation of leukocyte genomic DNA increases risk of colorectal cancer among women. Additional studies are needed to investigate the association between pre-diagnostic genomic DNA methylation level and colorectal cancer risk among diverse populations.
Highlights
One-carbon metabolism, or methyl-group metabolism, is a critical pathway in cancer epigenetics [1]
Abnormal one-carbon metabolism may result in general genomic hypomethylation, which may predispose an individual to the development of neoplasia [2]
We evaluated the influence of leukocyte genomic DNA methylation status and its interaction with one-carbon metabolism-related nutrients, genetic polymorphisms, and other factors on the risk of colorectal cancer in a nested case-control study within the Nurses’ Health Study (NHS)
Summary
One-carbon metabolism, or methyl-group metabolism, is a critical pathway in cancer epigenetics [1]. It comprises a network of interrelated biochemical reactions involved in the transfer of methyl groups from one compound to another, which among other effects can affect the level of DNA methylation. Abnormal one-carbon metabolism may result in general genomic (global) hypomethylation, which may predispose an individual to the development of neoplasia [2]. We evaluated the influence of leukocyte genomic DNA methylation status and its interaction with one-carbon metabolism-related nutrients, genetic polymorphisms, and other factors on the risk of colorectal cancer in a nested case-control study within the Nurses’ Health Study (NHS). Abnormal one-carbon metabolism may lead to general genomic (global) hypomethylation, which may predispose an individual to the development of colorectal neoplasia
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