ADOLESCENT DIET, HORMONES AND BREAST CANCER SUSCEPTIBILITY (DISC 06)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 儿童饮食干预研究（DISC）是一项多中心、随机对照临床试验，旨在评估青春期减脂饮食干预对随机分组时8-10奥尔兹健康女孩血清性激素的影响。 经过五年的参与，与常规护理组的女孩相比，干预组的女孩在月经周期的卵泡期的雌二醇和非SHBG结合雌二醇显著降低30%，雌酮降低21%，硫酸雌酮水平降低29%。 七年后，雌激素的差异不再明显，但干预组的女孩与常规护理组的女孩相比，黄体期孕酮水平显着降低了53%。 这些发现表明，DISC干预改变了下丘脑-垂体-卵巢（HPO）轴的功能。 虽然目前尚不清楚这些变化是否会最终影响参与者成年后患乳腺癌的风险，但雌二醇和孕酮都是调节青春期乳腺发育的乳腺有丝分裂原。 虽然其患病率随着年龄的增长而增加，但一些数据表明代谢综合征可能也起源于儿童和青少年。 代谢综合征与冠状动脉疾病和2型糖尿病的发生有关，并可能与乳腺癌的风险有关。 代谢综合征与肥胖密切相关，饮食可能在其病因中起作用。 这些研究人员将在DISC参与者中评估DISC干预在青春期对与乳腺癌风险相关的生物标志物的影响，包括血清激素水平，乳腺密度和骨矿物质密度。 这项研究将大大提高对乳腺发育的理解，并可能提高对乳腺癌和代谢综合征起源的理解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Dietary Intervention Study in Children (DISC) was a multicenter, randomized controlled clinical trial that evaluated the effect of a reduced fat dietary intervention during puberty on serum sex hormones in girls who were healthy 8-10 year olds at randomization. After five years of participation, girls in the intervention group had significantly 30% lower estradiol and non-SHBG bound estradiol, 21% lower estrone, and 29% lower estrone sulfate levels during the follicular phase of their menstrual cycles compared to girls in the usual care group. After seven years, differences in estrogens were no longer apparent, but girls in the intervention group had significantly, 53%, lower luteal phase progesterone levels compared to girls in the usual care group. These findings suggest that the DISC intervention altered function of the hypothalamic-pituitary-ovarian (HPO) axis. Although it is currently unknown whether these changes will ultimately influence participants' risk of developing breast cancer as adults, estradiol and progesterone are both breast mitogens that regulate breast development during puberty. Although its prevalence increases with increasing age, some data suggest that the metabolic syndrome may have its roots in childhood and adolescence as well. Metabolic syndrome is associated with development of coronary artery disease and type 2 diabetes and may be related to risk of breast cancer. Metabolic syndrome is closely linked to obesity, and diet likely plays a role in its etiology. These investigators will evaluate in DISC participants, who are now in their twenties, the effect of the DISC intervention during puberty on biomarkers associated with breast cancer risk including serum hormone levels, breast density, and bone mineral density. This study will greatly improve understanding of breast development and possibly the origins of breast cancer and the metabolic syndrome.