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White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)
White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)
- Source :
- Breast Cancer Research, Vol 19, Iss 1, Pp 1-11 (2017), Breast Cancer Research : BCR
- Publication Year :
- 2017
- Publisher :
- BMC, 2017.
-
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.
- Subjects :
- Male
0301 basic medicine
CA15-3
Oncology
medicine.medical_specialty
Lung Neoplasms
Colorectal cancer
Breast Neoplasms
lcsh:RC254-282
Breast Neoplasms, Male
03 medical and health sciences
Prostate cancer
0302 clinical medicine
Breast cancer
Risk Factors
Internal medicine
Biomarkers, Tumor
Leukocytes
medicine
Humans
Lung cancer
Ovarian Neoplasms
Clinical Trials as Topic
Global DNA methylation
%5mdC
business.industry
Cohort
Prostatic Neoplasms
Cancer
DNA Methylation
Neoplastic Cells, Circulating
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
030104 developmental biology
030220 oncology & carcinogenesis
DNA methylation
White blood cells
Female
Colorectal Neoplasms
business
Ovarian cancer
Research Article
Subjects
Details
- Language :
- English
- Volume :
- 19
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Breast Cancer Research
- Accession number :
- edsair.doi.dedup.....ecded8d8a9ed01de88ccbe9bd3b55169
- Full Text :
- https://doi.org/10.1186/s13058-017-0886-6