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AS584 - Epigenetic Age as a Marker of Reproductive Age and Modifier of Invasive Breast Cancer Risk among Postmenopausal Women
[This page is intended to provide a study summary, the sections of which are below. Please complete these sections, as applicable. The headings below are suggested headings. You can remove inapplicable sections, or add new ones relevant to your study]
Investigator Names and Contact Information
Alexandra Binder [abinder@ucla.edu]
Introduction/Intent
Epigenetic age is a predictor of total cancer risk and mortality. An
indicator of biological aging, epigenetic age is suggested to capture the
influence of lifestyle and environmental exposures across the life course on
cellular function. Among postmenopausal women, many predictors of cancer
incidence are related to reproductive history. A few of the factors associated
with an increased hazard of breast, endometrial and ovarian cancer in
postmenopausal women have demonstrated to decelerate epigenetic aging. This is
in contrast to prior studies of lung and total cancer incidence, which suggest
that accelerated epigenetic aging is associated with increased cancer risk and
mortality. 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
within approximately 5,000 postmenopausal
women from the Women’s Health Initiative (WHI) Observational Study and the
control arm of the Clinical Trial with previously measured genome-wide
methylation data (Ancillary Studies: AS311, AS315, BA23). This will include a
subset of 1,382 women with bioavailable
estradiol measurements, and 285 cases of invasive breast cancer. Epigenetic age
acceleration (AgeAccel; deviance between chronological
and epigenetic age) will be estimated in whole blood. 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.
Specific Aims
- Characterize the variation in AgeAccel associated with reproductive history (e.g. age of menarche, age of first birth, and oral contraceptive use)
- Assess how AgeAccel is influenced by modifiable lifestyle factors associated with hormonally responsive cancer risk among postmenopausal women
- Analyze the association between AgeAccel and postmenopausal bioavailable estradiol
- Investigate how endogenous hormone levels may mediate and interact with modifiable and unmodifiable predictors of postmenopausal cancer risk to influence AgeAccel
- Estimate the impact of AgeAccel on the hazard of postmenopausal invasive breast cancer and evaluate its utility for improving risk prediction models
