Publication Date
2017
Journal or Book Title
Breast Cancer Research
Abstract
Background
Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk.
Methods
To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. A total of 428 invasive breast cancer cases and 419 controls, frequency matched on age at entry (55–59, 60–64, 65–69, ≥70 years), year of entry (on/before September 30, 1997, on/after October 1, 1997) and period of DNA extraction (previously extracted, newly extracted) were included. The ratio of 5-methyl-2’ deoxycytidine [5-mdC] to 2’-deoxyguanine [dG], assuming [dG] = [5-mdC] + [2’-deoxycytidine [dC]] (%5-mdC), was determined by liquid chromatography-electrospray ionization-tandem mass spectrometry, an especially accurate method for assessing total genomic DNA methylation.
Results
Odds ratio (OR) estimates and 95% confidence intervals (CI) for breast cancer risk adjusted for age at entry, year of entry, and period of DNA extraction, were 1.0 (referent), 0.89 (95% CI, 0.6–1.3), 0.88 (95% CI, 0.6–1.3), and 0.84 (95% CI, 0.6–1.2) for women in the highest compared to lowest quartile levels of %5md-C (p for trend = .39). Effects did not meaningfully vary by time elapsed from WBC collection to diagnosis.
Discussion
These results do not support the hypothesis that global DNA hypomethylation in WBC DNA is associated with increased breast cancer risk prior to the appearance of clinical disease.
DOI
https://doi.org/10.1186/s13058-017-0886-6
Volume
19
License
UMass Amherst Open Access Policy
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Recommended Citation
Sturgeon, Susan R.; Pilsner, J. Richard; Arcaro, Kathleen F.; Ikuma, Kaoru; Wu, Haotian; Kim, Soon-Mi; Chopra-Tandon, Nayha; Karpf, Adam R.; Ziegler, Regina G.; Schairer, Catherine; Balasubramanian, Raji; and Reckhow, David A., "White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)" (2017). Biostatistics and Epidemiology Faculty Publications Series.
19
https://doi.org/10.1186/s13058-017-0886-6