Use of dietary botanicals for maintaining health can be greatly enhanced through elucidation of their effects on
epigenetic mechanisms, their combined impact and their efficacy at different life stages, especially early in life.
Epigenetic aberrations often alter key gene expressions that are crucial in maintaining health and delaying the
onset and reducing the impact of cancer. However, very little is known with respect to the impact of dietary
botanicals consumed in combination early in life on epigenetic mechanisms and the risk of developing cancer.
Our studies have indicated that green tea polyphenols (GTPs) and sulforaphane (SFN)-rich broccoli sprouts
(BSp), administered in combination at safe levels consumable by humans, are highly effective in increasing
cancer latency in mice that spontaneously develop estrogen receptor (ER)-negative [ER(-)] breast cancer and
that this may be more effective when administered early in life. It is important that although most ER(+) breast
cancer is relatively highly responsive to therapy once it forms, ER(-) breast cancer has high mortality rates if it
is not prevented from developing. Therefore, cancer prevention approaches that reduce ER(-) breast cancer
will have by far the greatest impact on the incidence of cancer fatalities. Our results indicate that the efficacy
of this dietary approach depends on the ability of these botanicals to significantly impact epigenetic gene
regulation. Our hypothesis is that early life consumption of combined GTPs and BSp is highly effective in
neutralizing epigenomic alterations and epigenetic control of key genes that lead to ER(-) BC formation and
progression. These studies will be important to determine the efficacy of botanicals at various stages of life so
that their consumption will optimize the potential for cancer prevention. We do not yet fully understand the
epigenetic mechanisms of these botanicals consumed at different stages of life and especially in combination
as they are often consumed. Further, the impact of these botanicals on global epigenomic processes at
various ages is not yet known. A major goal of this proposed investigation is to confront these persistent
challenges. The incorporation of these botanicals into diets of the young is safe and could lead to important
revisions of dietary regimens to increase cancer latency and to significantly reduce the incidence of ER(-)
breast cancer fatalities. Novel techniques such as chromatin immunoprecipitation-genomic bisulfite sequencing
(ChIP-GBS) that we invented as well as several advanced epigenomic technologies will be employed.
Elucidation of the epigenetic mechanisms for cancer latency and reducing the risk of cancer will result in
significant increases in the health of hundreds of thousands of individuals worldwide. This investigation will
also provide essential information for identification of epigenetic biomarkers of breast cancer at different stages
of life that will facilitate elucidation of the predisposition, diagnosis and prognosis of breast cancer. Most
importantly, the use of safe and effective epigenetic aberration-neutralizing botanicals in early life has high
translational potential for increasing the latency and reducing the impact of ER(-) breast cancer.