Fruit and vegetable intervention in lactating women to reduce breast cancer risk: effects on breast cell DNA methylation, breast inflammation, and weight

项目概要/摘要 水果和蔬菜干预哺乳期妇女降低乳腺癌风险：对乳腺细胞的影响 DNA甲基化、乳腺炎和体重 机理数据表明，水果和蔬菜中的化合物具有抗炎和抗癌作用 可以降低乳腺癌风险的特性。然而，观察性和干预性研究提供了 结果喜忧参半，美国癌症研究所（AICR）最近的一份报告得出结论， 数据不足，但表明非淀粉类蔬菜和含类胡萝卜素的食物可降低风险。 测量误差，研究人群中富含类胡萝卜素的水果和蔬菜摄入量相对较低， 强调成年后的饮食，和混杂因素可能有助于弱关联。 因此，我们将在年轻女性中进行一项随机饮食干预试验，以评估 每天至少8到10份深色素和营养丰富的水果和蔬菜减少生物标志物 乳腺癌的风险。干预的重点是母乳喂养的妇女，因为：1）怀孕和 哺乳是正常的早期生命过程事件; 2）妊娠相关乳腺癌（PABC）的风险是 产后10年内增加; 3）饮食干预，以扭转有害的分子变化 与青春期和怀孕相关的是更有可能在年轻女性比老年女性成功; 4）a 假设富含水果和蔬菜的饮食可以减少哺乳/断奶期间的炎症， PABC风险; 5）产后哺乳期妇女可能是一个高度积极的人群; 6）母乳提供 进入乳腺微环境和乳腺上皮细胞，以非侵入性地评估饮食干预 直接在乳房上。400名哺乳期母亲将被随机分配到干预组， 他们被要求在一年内将水果和蔬菜的摄入量增加到每天至少8到10份，或者 一个控制条件，参与者接受母乳喂养母亲的饮食指南。妇女 干预组将在前20周接受咨询和一盒水果和蔬菜， 他们会继续接受辅导。母乳中DNA甲基化和细胞因子谱的变化将被 评估。将监测母体体重和体脂分布以及婴儿生长。这些结果将 极大地扩展了我们对饮食如何改变特定器官中分子通路的知识，最终有助于 乳腺癌的病因和预防。此外，在乳房中观察到的客观有利结果 年轻女性的肥胖可能有助于旨在降低风险的重要行为改变。

Project Summary/Abstract Fruit and vegetable intervention in lactating women to reduce breast cancer risk: effects on breast cell DNA methylation, breast inflammation, and weight Mechanistic data show that compounds in fruits and vegetables have anti-inflammatory and anti-carcinogenic properties that can reduce breast cancer risk. However, observational and interventional studies have provided mixed results, and a recent report by the American Institute for Cancer Research (AICR) concludes that the data are insufficient but suggestive that non-starchy vegetables and foods containing carotenoids reduce risk. Measurement error, relatively low levels of carotenoid-rich fruit and vegetable intake in the study populations, emphasis on diet in later adulthood, and confounding factors likely contribute to the weak associations. Therefore, we will conduct a randomized diet intervention trial in young women to assess the extent to which at least 8 to 10 daily servings of deeply pigmented and nutrient dense fruits and vegetables reduces biomarkers of breast cancer risk. The intervention is focused on breastfeeding women because: 1) pregnancy and lactation are normal early life course events; 2) the risk of pregnancy-associated breast cancer (PABC) is increased for up to 10 years postpartum; 3) a dietary intervention to reverse the detrimental molecular changes associated with puberty and pregnancy is more likely to be successful in younger than in older women; 4) a diet rich in fruits and vegetables is hypothesized to reduce the inflammation during lactation/weaning and lower PABC risk; 5) postpartum lactating women may be a highly motivated population; and 6) breastmilk provides access to the breast microenvironment and breast epithelial cells to noninvasively assess the diet intervention directly in the breast. Four hundred nursing mothers will be randomly assigned to either the intervention arm, in which they are asked to increase fruit and vegetable intake to at least 8 to 10 daily servings for one year, or to a control condition in which participants receive a dietary guideline for breastfeeding mothers. Women in the intervention arm will receive counseling and boxes of fruits and vegetables for the first 20 weeks, after which they will continue to receive counseling. Changes in DNA methylation and cytokine profiles in breastmilk will be evaluated. Maternal weight and body fat distribution, and infant growth will be monitored. These results will greatly expand our knowledge of how diet alters molecular pathways in a specific organ, ultimately contributing to both breast cancer etiology and prevention. Additionally, objective favorable results observed in the breasts of young women can potentially contribute to important behavior changes aimed at reducing risk.