Calcium Intake and Colorectal Cancer Incidence and Survival

描述(申请人提供)：结直肠癌(CRC)仍然是美国女性和男性第三常见的癌症和与癌症相关的死亡。尽管总体证据支持钙在结直肠癌发生中的有益作用，但仍存在三个主要悬而未决的问题。首先，钙摄入预防结直肠癌的最佳剂量和时机尚不清楚。其次，尽管关于钙在风险中的作用的几种拟议机制也可能影响癌症的进展，但尚未有研究检验诊断后钙摄入是否会改善结直肠癌患者的存活率。最后，钙影响结直肠癌风险的生物学途径仍不清楚。由于未来的随机对照试验可能不可行来测试开始干预和CRC发病之间具有长时间或未知潜伏期的不同剂量，我们建议使用两个大的、特征良好的女性队列(护士健康研究，NHS)和男性(健康专业人员随访研究，HPFS)的资源来检验以下具体目标，在这两个队列中，分别自1980年和1986年以来每4年使用有效的食物频率问卷评估钙的摄入量。经过长达30年的随访，可以研究长期效果。目的1是探讨钙摄入预防结直肠癌的最佳剂量和时机。目的2是评估诊断后充足的钙摄入量是否与更好的CRC生存相关。目标3是利用已有的结直肠癌肿瘤的信使核糖核酸表达数据，发现钙可能起作用以降低结直肠癌风险的生物学途径。两项对女性和男性进行多项钙评估的大型队列研究和先前存在的有效的信使核糖核酸表达数据提供了一个独特的机会，以成本效益的方式解决拟议的目标。该项目的完成将对未来美国成年人预防结直肠癌和存活的钙摄入量饮食建议做出重要贡献。

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) remains the third most common cancer and cancer-related death in US women and men. Although the totality of evidence in aggregate supports a beneficial role of calcium in colorectal carcinogenesis, three major unresolved outstanding questions exist. First, the optimal dose and timing of calcium intake for CRC prevention remains unknown. Second, although several proposed mechanisms for calcium's role in risk may also influence cancer progression, no study has yet examined whether post-diagnostic calcium intake will improve survival among CRC patients. Lastly, the biological pathways by which calcium influences CRC risk remain unknown. Because future randomized controlled trials may not be feasible to test different doses with long or unknown latency between start intervention and CRC onset, we propose to examine the following specific aims using the resources of two large, well- characterized cohorts of women (the Nurses' Health Study, NHS) and men (the Health Professionals Follow-up Study, HPFS), in which calcium intake was assessed every 4 years since 1980 and 1986 respectively, using validated food frequency questionnaires. With up to 3 decades of follow-up, long-term effects can be studied. Aim 1 is to investigate the optimal dose and timing of calcium intake for CRC prevention. Aim 2 is to assess whether adequate post- diagnostic calcium intake is associated with better CRC survival. Aim 3 is to discover biological pathways through which calcium might operate to reduce risk of CRC using pre-existing mRNA expression data from the CRC tumors. Two large cohort studies of women and men with multiple calcium assessments and pre-existing validated mRNA expression data provide a unique opportunity to address the proposed aims in a cost-effective manner. Completion of this project will make important contributions towards informing future dietary recommendations of calcium intake for CRC prevention and survival in US adults.