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Association between global DNA hypomethylation in leukocytes and risk of breast cancer
Open accessAbstract
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 < or = 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.
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Cites
Epigenetic differences arise during the lifetime of monozygotic twins
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suñer, D., Cigudosa, J. C., Urioste, M., Benitez, J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500398102 · Cited by 3,602
Induction of tumors in mice by genomic hypomethylation
Gaudet, F., Hodgson, J. G., Eden, A., Jackson-Grusby, L., Dausman, J., Gray, J. W., Leonhardt, H., & Jaenisch, R. (2003) · Science · doi:10.1126/science.1083558 · Cited by 1,499 · cited 1×
“Hypomethylation has been proposed to contribute to malignancy by activating oncogenes (12,13), inducing genomic instability ( 14 ) and causing chromosome instability (4,15–17).”
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Cited by
DNA methylation in white blood cells: Association with risk factors in epidemiologic studies
Terry, M. B., Delgado-Cruzata, L., Vin-Raviv, N., Wu, H. C., & Santella, R. M. (2011) · Epigenetics · doi:10.4161/epi.6.7.16500 · Cited by 320
Influence of environmental exposure on human epigenetic regulation
Marsit, C. J. (2015) · Journal of Experimental Biology · doi:10.1242/jeb.106971 · Cited by 253
Metadata
- Authors
- 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.
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-07-07
- Volume
- 30
- Issue
- 11
- Pages
- 1889-1897
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2097156376
- Cited by
- 185
- References
- 2
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
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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. https://doi.org/10.1093/carcin/bgp143
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