Early life prevention of breast cancer with combined epigenetic botanicals

通过阐明膳食植物对人体健康的影响， 表观遗传机制、其综合影响及其在不同生命阶段，特别是生命早期的功效。 表观遗传畸变经常改变关键基因表达，这些基因表达对维持健康和延缓衰老至关重要。 减少癌症的影响。然而，关于饮食的影响知之甚少。 在生命早期联合食用植物药对表观遗传机制和患癌症风险的影响。 我们的研究表明，富含绿色茶多酚和萝卜硫素的西兰花芽 (BSp)，以人类可消耗的安全水平组合施用，在增加 自发发展雌激素受体（ER）阴性[ER（-）]乳腺癌的小鼠的癌症潜伏期， 在生命早期使用可能更有效。重要的是，尽管大多数ER（+）乳腺癌 癌症一旦形成，对治疗的反应相对较高，ER（-）乳腺癌如果 并没有阻止发展。因此，减少ER（-）乳腺癌的癌症预防方法 将对癌症死亡率产生最大的影响。我们的研究结果表明， 这种饮食方法的有效性取决于这些植物对表观遗传基因的影响 调控我们的假设是，生命早期服用GTP和BSP组合对治疗糖尿病非常有效。 中和导致ER（-）BC形成的关键基因的表观基因组改变和表观遗传控制， 进展这些研究对于确定植物药在生命的各个阶段的功效非常重要， 他们的消费将优化癌症预防的潜力。我们还没有完全理解 这些植物在生命的不同阶段，特别是在组合中消耗的表观遗传机制 因为它们经常被消费。此外，这些植物对全球表观基因组过程的影响， 年龄尚不清楚。这项拟议调查的一个主要目标是对抗这些持续存在的 挑战将这些植物纳入年轻人的饮食是安全的，并可能导致重要的 修改饮食方案，以增加癌症潜伏期并显著降低ER（-）的发病率 乳腺癌死亡人数染色质免疫沉淀-基因组亚硫酸氢盐测序等新技术 （ChIP-GBS）以及几种先进的表观基因组技术将被采用。 阐明癌症潜伏期的表观遗传机制和降低癌症风险将导致 全世界数十万人的健康状况得到显著改善。这次调查将 也为不同阶段乳腺癌表观遗传生物标志物的鉴定提供了必要的信息 这将有助于阐明乳腺癌的易感性、诊断和预后。最 重要的是，在生命早期使用安全有效的表观遗传异常中和植物药， 因此，本发明提供了增加ER（-）乳腺癌的潜伏期和降低ER（-）乳腺癌的影响的翻译潜力。

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.