# Combinatorial epigenetic-based prevention of breast cancer

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $344,164

## Abstract

Combinatorial dietary approaches to prevent highly fatal estrogen receptor-negative [ER(-)] breast cancer
(BC) can offer many advantages over single-agent approaches, most notably the potential for greater efficacy
without increased risk of toxicity. We have shown that combined green tea polyphenols that inhibit DNA
methyltransferases and sulforaphane in broccoli sprouts that inhibits histone deacetylases can significantly
delay ER(-) BC initiation and impede its progression at practical and safe dietary levels. Our results have also
shown that the epigenetic machinery is mechanistically important to the efficacy of ER(-) BC prevention
by these diets. Maternal or paternal consumption of this combinatorial regimen can lead to increased latency
and reduced tumor growth in ER(-) BC offspring that have consumed a control diet. Our field-driving studies
show for the first time that this combinatorial diet impacts the epigenome and gene expression of gametes
strongly supporting transgenerational epigenetic effects. Our hypothesis is that combinatorial green tea
polyphenols and sulforaphane-enriched broccoli sprout diets can extend their epigenetic-neutralizing ER(-) BC
preventive effects from one generation to another either through transplacental effects or through
transgenerational effects. These studies will be important to resolving the generational efficacy of
combinatorial cancer prevention and the epigenetic mechanisms through which this effect is mediated. Since
our preliminary findings have indicated that consumption of this combinatorial diet can operate through the
paternal as well as maternal lineage to prevent ER(-) BC in control-fed female offspring, this strongly suggests
that the gametogenic epigenetic changes we have discovered have mechanistic importance for
transgenerational effects in addition to transplacental effects in mothers fed this combinatorial diet. The
paternal effects on epigenetic control of key tumor-related genes by this combinatorial epigenetic-modulating
diet will contribute significantly to elucidation of the mechanisms through which this diet confers preventive
effects on ER(-) BC. One of the goals of this proposed innovative investigation is to resolve the generational
ER(-) BC cancer preventive impact of combinatorial epigenetic-modulating green tea polyphenols and
sulforaphane-enriched broccoli sprouts and the epigenetic and epigenomic mechanisms responsible for their
efficacy. This proposed investigation will have considerable impact in that the consumption of a combined
epigenetic-modulating diet by either the mother or father to delay and reduce ER(-) BC in their offspring would
have broad implications for new perspectives for cancer prevention. Further, ER(-) BC is often recalcitrant to
conventional modes of cancer therapy which significantly increases the importance of means to facilitate its
prevention. Novel approaches to reducing the risk of ER(-) BC through maternal and/or paternal
consumption of this c...

## Key facts

- **NIH application ID:** 10120206
- **Project number:** 2R01CA178441-06A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** TRYGVE O TOLLEFSBOL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $344,164
- **Award type:** 2
- **Project period:** 2014-04-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120206

## Citation

> US National Institutes of Health, RePORTER application 10120206, Combinatorial epigenetic-based prevention of breast cancer (2R01CA178441-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10120206. Licensed CC0.

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