Mechanisms Linking Dairy to Higher Prostate Cancer Risk

描述(由申请人提供)： 在以前的研究中，乳制品的摄入量与前列腺癌有关，而牛奶摄入量与前列腺癌死亡率之间的生态相关性可能比包括总脂肪在内的任何其他饮食因素都要强。乳制品增加风险的机制尚不清楚，但包括两种可能性。首先，奶制品可能会提高循环中胰岛素样生长因子I(IGF-I)的水平，这可能是前列腺癌的一个危险因素。其次，乳制品钙可能会抑制循环中潜在防癌的1，25-羟基维生素D(1，25-D)水平。其他证据表明，乳制品对1，25-D水平的影响可能因种族和维生素D状况而有所不同。这项拟议的工作将评估这两个假说，作为对观察到的乳制品和前列腺癌风险之间的关联的可能解释。我们试图验证这样的假设，即乳制品摄入量增加IGF-I水平但降低循环中的1，25-D水平，这种影响是由乳制品中可测量的饮食因素介导的，并且对1，25-D水平的影响因种族和维生素D状况而不同。研究人群将包括参加福克斯·蔡斯癌症中心前列腺癌风险评估计划(PRAP)的545名男性，时间为7/00至6/07。如果男性年龄在35岁到69岁之间，没有前列腺癌病史，对于非非洲裔美国人男性，至少有一个患有前列腺癌的一级亲属，就符合条件；非裔美国人男性不需要有家族史，因为他们的风险已经很高了。非裔美国人男性约占样本的一半。在注册时，男性提供血样和完整的饮食和健康史问卷。实验室分析将包括评估血浆IGF-I、胰岛素样生长因子结合蛋白-3、25-羟基维生素D和1，25-D的水平。这些将与乳制品和作为潜在介体的感兴趣的营养物质有关，如蛋白质、钙和其他矿物质。我们还将研究根据种族和维生素D状态对乳制品-1，25-D关联的可能影响修改。鉴于观察乳制品对健康的不良影响的巨大影响，更好地了解乳制品可能增加前列腺癌风险的机制至关重要，为支持简单但可能存在争议的预防策略提供生物学证据是至关重要的。研究结果还将提供对非裔美国人至关重要的信息，对他们来说，减少乳制品的建议可能是有害的，而不是有益的。

DESCRIPTION (provided by applicant): Dairy food intake has been associated with prostate cancer in previous work, and the ecologic correlation between milk intake and prostate cancer mortality may be stronger than for any other dietary factor, including total fat. The mechanism by which dairy increases risk is unknown but includes two possibilities. First, dairy may elevate circulating levels of insulin-like growth factor I (IGF-I), a likely risk factor for prostate cancer. Second, dairy calcium may suppress circulating levels of potentially cancer-protective 1,25-hydroxyvitamin D (1,25-D). Other evidence suggests a possible difference in a dairy effect on 1,25-D levels by ethnicity and vitamin D status. The proposed work will evaluate the two hypotheses as possible explanations for observed associations between dairy and prostate cancer risk. We seek to test the hypotheses that dairy intake increases IGF-I levels but reduces circulating 1,25-D levels, that the effects are mediated by measurable dietary factors in dairy, and that effects on 1,25-D levels differ by ethnicity and vitamin D status. The study population will include 545 men enrolled in the Fox Chase Cancer Center Prostate Cancer Risk Assessment Program (PRAP) from 7/00 to 6/07. Men are eligible if they are 35-69 years old, have no history of prostate cancer, and, for non-African American men, have at least one 1st-degree relative with prostate cancer; no family history is required for African American men, who make up about half of the sample, because of their already elevated risk. Upon enrollment, men provide a blood sample and complete diet and health history questionnaires. Laboratory analyses will include assessments of plasma levels of IGF-I, insulin-like growth factor binding protein-3, 25-hydroxyvitamin D, and 1,25-D. These will be examined in relation to dairy foods and nutrients of interest as potential mediators, such as protein, calcium, and other minerals. We will also examine possible effect modification of the dairy-1,25-D association by ethnicity and vitamin D status. Given the enormous implications of observing an adverse health effect for dairy foods, a better understanding of the mechanisms by which dairy might increase prostate cancer risk is essential, providing biologic evidence to support a simple but potentially controversial preventive strategy. Findings will also provide information critical to African Americans, for whom a recommendation to reduce dairy may be harmful rather than beneficial.