Association between global DNA hypomethylation in leukocytes and risk of breast cancer

Ji Yeob Choi, Smitha R. James, Petra A. Link, Susan E. Mccann, Chi Chen Hong, Warren Davis, Mary K. Nesline, Christine B. Ambrosone, Adam R. Karpf

Research output: Contribution to journalArticle

145 Scopus citations

Abstract

Background: Global DNA hypomethylation may result in chromosomal instability and oncogene activation, and as a surrogate of systemic methylation activity, may be associated with breast cancer risk. Methods: Samples and data were obtained from women with incident early-stage breast cancer (I-IIIa) and women who were cancer free, frequency matched on age and race. In preliminary analyses, genomic methylation of leukocyte DNA was determined by measuring 5-methyldeoxycytosine (5-mdC), as well as methylation analysis of the LINE-1-repetitive DNA element. Further analyses used only 5-mdC levels. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of breast cancer in relation to amounts of methylation. Results: In a subset of samples tested (n = 37), 5-mdC level was not correlated with LINE-1 methylation. 5-mdC level in leukocyte DNA was significantly lower in breast cancer cases than healthy controls (P = 0.001), but no significant case-control differences were observed with LINE-1 methylation (P = 0.176). In the entire data set, we noted significant differences in 5-mdC levels in leukocytes between cases (n = 176) and controls (n = 173); P value <0.001. Compared with women in the highest 5-mdC tertile (T3), women in the second (T2; OR = 1.49, 95% CI = 0.84-2.65) and lowest tertile (T1; OR = 2.86, 95% CI = 1.65-4.94) had higher risk of breast cancer (P for trend ≤0.001). Among controls only and cases and controls combined, only alcohol intake was found to be inversely associated with methylation levels. Conclusion: These findings suggest that leukocyte DNA hypomethylation is independently associated with development of breast cancer.

Original languageEnglish (US)
Pages (from-to)1889-1897
Number of pages9
JournalCarcinogenesis
Volume30
Issue number11
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Cancer Research

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    Choi, J. Y., James, S. R., Link, P. A., Mccann, S. E., Hong, C. C., Davis, W., Nesline, M. K., Ambrosone, C. B., & Karpf, A. R. (2009). Association between global DNA hypomethylation in leukocytes and risk of breast cancer. Carcinogenesis, 30(11), 1889-1897. https://doi.org/10.1093/carcin/bgp143