# Epigenetic Age as a Marker of Reproductive Age and Modifier of Invasive Breast Cancer Risk Among Postmenopausal Women

> **NIH NIH K07** · UNIVERSITY OF HAWAII AT MANOA · 2020 · $145,657

## Abstract

Dr. Binder's goal is to become a leading academic epidemiologist in the epigenetic programming of health and
disease, with an emphasis on hormonally responsive cancer risk. She plans to apply innovative methodological
approaches to efficiently capture biologically meaningful changes in gene regulation. Dr. Binder will collaborate
with a broad spectrum of scientists to translate insight from these mechanistic studies into improvements in
health care and disease prevention. Her research thus far has focused on determinants of epigenetic patterns
established in utero and during puberty. The proposed research project will bridge this experience to study the
impact of epigenetic modifications acquired across the life course on postmenopausal breast cancer incidence.
Epigenetic age is a predictor of health and an indicator of biological aging, capturing the cumulative impact of
environmental and behavioral influences across time on cellular function. Prior studies have suggested a positive
correlation between epigenetic aging and cancer risk. Paradoxically, aspects of reproductive history suggested
to decelerate epigenetic age are associated with increased breast cancer incidence. Therefore we hypothesize
there is a clinically relevant interaction between epigenetic age and the process of reproductive aging on
hormonally responsive cancer risk among postmenopausal women. We propose analyzing epigenetic age
acceleration (AgeAccel; deviance between chronological and epigenetic age) within 5,406 postmenopausal
women from the Women's Health Initiative Observational Study and Clinical Trial with previously measured
genome-wide DNA methylation in whole blood. This will include a subset of 1,382 women with bioavailable
estradiol measurements, and 285 cases of invasive breast cancer. We plan to (1) characterize the variation in
AgeAccel associated with reproductive history, (2) assess how AgeAccel is influenced by lifestyle factors, (3)
analyze the association between AgeAccel and bioavailable estradiol and testosterone, (4) investigate how these
hormones may mediate and interact with modifiable and unmodifiable predictors of cancer risk to impact
AgeAccel, and (5) estimate the association between AgeAccel and breast cancer hazard. Together these aims
will separate the influences on biological aging from chronological age relevant for cancers associated with
reproductive history among postmenopausal women. Additionally, this work will appraise the utility of AgeAccel
to track the change in risk profile over time. To conduct this research, Dr. Binder will build her substantive
knowledge of aging and postmenopausal health through organized mentorships, didactic coursework, affiliations
with interdisciplinary research institutes and associated seminars. Furthermore, Dr. Binder will generate new
research partnerships with experts in cancer control and prevention to inform her analytic approach and
interpretations. This development plan will build Dr. Binder's repu...

## Key facts

- **NIH application ID:** 9976475
- **Project number:** 5K07CA225856-04
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Alexandra Margaret Lynn Binder
- **Activity code:** K07 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $145,657
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976475

## Citation

> US National Institutes of Health, RePORTER application 9976475, Epigenetic Age as a Marker of Reproductive Age and Modifier of Invasive Breast Cancer Risk Among Postmenopausal Women (5K07CA225856-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9976475. Licensed CC0.

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