Adolescent Diet, Hormones & Breast Cancer Susceptibility

背景：动物和生态学研究强烈支持饮食在乳腺癌病因学中的作用，但病例对照和队列研究结果不明确。乳房的快速生长和成熟发生在青春期，女性在青春期的饮食可能比成年后的饮食更能影响她患乳腺癌的风险。儿童饮食干预研究（DISC）是一项随机对照临床试验，评估青春期低脂饮食干预对301名8-10岁健康女孩血清性激素的影响。参与5年和7年后，干预组与常规护理组相比，卵泡期血清雌二醇水平显著降低30%，黄体期黄体酮水平显著降低53%。雌二醇和黄体酮是调节青春期乳房发育的乳房分裂原，这些差异可能会影响参与者成年后患乳腺癌的风险。我们建议利用这个独特的机会来评估青春期饮食干预对与乳腺癌风险相关的生物标志物的影响，以提高我们对乳房发育和乳腺癌起源的理解。具体目的：我们的主要目的是确定DISC干预对成年早期血清黄体酮水平的长期影响。次要目的是确定DISC干预对成年早期血清雌二醇水平、骨密度和乳腺密度的影响。设计：对参与DISC的301名20多岁的女孩进行随访。将收集人口统计、病史、月经和生育史、身体活动和饮食方面的数据。将测量身高和体重、血清黄体酮和雌二醇水平、骨密度和乳腺密度。意义：作为对照临床试验的一部分，该研究将通过对血清激素、乳腺密度和骨密度的影响来确定青春期饮食对乳腺癌风险的影响。这些生物标志物是乳腺癌的三个最强风险因素，很容易受到青少年饮食的影响。因为饮食是一个可改变的风险因素，这项研究的结果可以用来制定预防策略。

DESCRIPTION (provided by applicant): Background: Animal and ecologic studies strongly support a role of diet in breast cancer etiology, but case-control and cohort study results are equivocal. Rapid growth and maturation of the breasts occurs during adolescence, and a woman's diet as an adolescent may affect her risk of developing breast cancer more than her diet as an adult. The Dietary Intervention Study in Children (DISC) was a randomized controlled clinical trial that evaluated the effect of a reduced fat diet intervention during puberty on serum sex hormones in 301 girls who were healthy 8-10 year olds at randomization. After 5 and 7 years of participation, respectively, the intervention group had significantly 30% lower follicular phase serum estradiol and 53% lower luteal phase progesterone levels compared to the usual care group. Estradiol and progesterone are breast mitogens that regulate breast development during puberty and these differences could potentially influence participants' risk of developing breast cancer as adults. We propose to take advantage of this unique opportunity to evaluate the effect of a diet intervention during adolescence on biomarkers associated with breast cancer risk to improve our understanding of breast development and the origins of breast cancer. Specific Aims: Our primary aim is to determine the long-term effect of the DISC intervention on serum progesterone levels in early adulthood. Secondary aims are to determine the effects of the DISC intervention on serum estradiol levels, bone mineral density, and breast density in early adulthood. Design: A follow-up visit will be conducted with the 301 girls who participated in DISC and who are now in their twenties. Data will be collected on demographics, medical history, menstrual and reproductive history, physical activity, and diet. Heights and weights, serum progesterone and estradiol levels, bone mineral density, and breast density will be measured. Significance: The proposed study will determine, as part of a controlled clinical trial, the effects of diet during adolescence on breast cancer risk via effects on serum hormones, breast density, and bone mineral density. These biomarkers are three of the strongest risk factors for breast cancer and could readily be affected by adolescent diet. Because diet is a modifiable risk factor, results of this proposed study could be used to develop strategies for prevention.