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J Natl Cancer Inst. 2019 Feb 22. pii: djz020. doi: 10.1093/jnci/djz020. [Epub ahead of print]

Methylation-based biological age and breast cancer risk.

Author information

1
Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC.
2
Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC.
3
Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC.

Abstract

BACKGROUND:

Age is one of the strongest predictors of cancer, chronic disease and mortality, but biological responses to aging differ among people. Epigenetic DNA modifications have been used to estimate "biological age," which may be a useful predictor of disease risk. We test this hypothesis for breast cancer.

METHODS:

Using a case-cohort approach, we measured baseline blood DNA methylation of 2,764 women enrolled in the Sister Study, 1,566 of whom subsequently developed breast cancer after an average of six years. Using three previously established methylation-based "clocks" (Hannum, Horvath, and Levine) we defined biological age acceleration for each woman by comparing her estimated biological age with her chronological age. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer risk were estimated using Cox regression models. All statistical tests were two-sided.

RESULTS:

Each of the three clocks showed that biological age acceleration was statistically significantly associated with increased risk of developing breast cancer (5 year age acceleration, Hannum's clock: HR = 1.10, 95% CI: 1.00, 1.21, P= 0.04; Horvath's clock: HR = 1.08, 95% CI: 1.00, 1.17, P= 0.04; Levine's clock: HR: 1.15, 95% CI: 1.07, 1.23, P < 0.001 ). For Levine's clock, each five-year acceleration in biological age corresponded with a 15% increase in breast cancer risk. Although biological age may accelerate with menopausal transition, age acceleration in premenopausal women independently predicted breast cancer. Case-only analysis suggested that, among women who develop breast cancer, increased age acceleration is associated with invasive cancer (OR for invasive=1.09, 95% CI: 0.98, 1.22, P = 0.10).

CONCLUSIONS:

DNA methylation-based measures of biological age may be important predictors of breast cancer risk.

KEYWORDS:

DNA methylation; aging; biological age; breast cancer; epigenetic clock

PMID:
30794318
DOI:
10.1093/jnci/djz020

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