Pre-Diagnostic Leukocyte Genomic DNA Methylation and the Risk of Colorectal Cancer in Women

Hongmei Nan, Edward L. Giovannucci, Kana Wu, Jacob Selhub, Ligi Paul, Bernard Rosner, Charles S. Fuchs, Eunyoung Cho

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: Abnormal one-carbon metabolism may lead to general genomic (global) hypomethylation, which may predispose an individual to the development of colorectal neoplasia. Methods: We 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. Results: Overall 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). Conclusions: We 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.

Original languageEnglish (US)
Article numbere59455
JournalPLoS One
Volume8
Issue number4
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

Fingerprint

DNA methylation
DNA Methylation
colorectal neoplasms
Colorectal Neoplasms
leukocytes
Leukocytes
genomics
Metabolism
Carbon
Association reactions
metabolism
carbon
Plasmas
odds ratio
confidence interval
risk factors
Odds Ratio
Confidence Intervals
Methylation
Liquid chromatography

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Nan, H., Giovannucci, E. L., Wu, K., Selhub, J., Paul, L., Rosner, B., ... Cho, E. (2013). Pre-Diagnostic Leukocyte Genomic DNA Methylation and the Risk of Colorectal Cancer in Women. PLoS One, 8(4), [e59455]. https://doi.org/10.1371/journal.pone.0059455

Pre-Diagnostic Leukocyte Genomic DNA Methylation and the Risk of Colorectal Cancer in Women. / Nan, Hongmei; Giovannucci, Edward L.; Wu, Kana; Selhub, Jacob; Paul, Ligi; Rosner, Bernard; Fuchs, Charles S.; Cho, Eunyoung.

In: PLoS One, Vol. 8, No. 4, e59455, 01.04.2013.

Research output: Contribution to journalArticle

Nan, H, Giovannucci, EL, Wu, K, Selhub, J, Paul, L, Rosner, B, Fuchs, CS & Cho, E 2013, 'Pre-Diagnostic Leukocyte Genomic DNA Methylation and the Risk of Colorectal Cancer in Women', PLoS One, vol. 8, no. 4, e59455. https://doi.org/10.1371/journal.pone.0059455
Nan, Hongmei ; Giovannucci, Edward L. ; Wu, Kana ; Selhub, Jacob ; Paul, Ligi ; Rosner, Bernard ; Fuchs, Charles S. ; Cho, Eunyoung. / Pre-Diagnostic Leukocyte Genomic DNA Methylation and the Risk of Colorectal Cancer in Women. In: PLoS One. 2013 ; Vol. 8, No. 4.
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