Circulating Vitamin D Levels and Risk of Breast and Colorectal Cancer: a Pooled A

描述（由申请人提供）：我们建议在15项队列研究中对循环25-羟基维生素D [25(OH)D]水平与乳腺癌和结直肠癌风险之间的关系进行前瞻性汇总分析。我们假设较高水平的循环25(OH)D水平与降低结直肠癌和乳腺癌的风险有关。据推测，这些关联在较瘦的个体、体力活动较多的个体和钙摄入量较高的个体中更为强烈。入选标准是采用前瞻性研究设计，前瞻性采集血液样本，至少有50例被分析的特定癌症病例。该联盟的15项研究分别在北美（n=10）、欧洲（n=4）和亚洲（n=1）进行，包括5061例结直肠癌病例和6817例乳腺癌病例，这些病例的循环25(OH)D水平已经或将被测量（主要作为本提案的一部分）。我们将分析每项研究的主要数据，以便在研究中对循环25(OH)D水平和混杂变量进行一致的建模。这将减少由于在已发表的文献中遇到的不同分析方法而导致的研究间异质性的潜在来源，并允许对循环25(OH)D水平的不同分类进行检查。我们还将能够评估在人群亚组、其他生化危险因素和肿瘤亚型之间是否存在关联，这些在已发表文献的荟萃分析中无法充分评估。此外，七个研究将产生新的数据，这将减少发表偏倚的影响。该提案充分利用了在世界各地收集的大量数据，以研究人员的专业知识和已建立的合作为基础，并利用了该项目的统计力量。这些分析将为维生素D与乳腺癌和结直肠癌风险之间的关系提供有力的见解。研究结果有可能为有关阳光照射和维生素D摄入需求的建议提供信息，并有助于减轻癌症负担。

DESCRIPTION (provided by applicant): We propose to conduct a prospective, pooled analysis of the association between circulating 25- hydroxyvitamin D [25(OH)D] levels and risk of breast and colorectal cancer within a consortium of 15 cohort studies. We hypothesize that higher levels of circulating 25(OH)D levels are associated with a reduced risk of colorectal and breast cancer. These associations are hypothesized to be stronger among leaner individuals, among more physically active individuals, and among individuals with higher calcium intakes. Inclusion criteria for participation in the consortium are that a study used a prospective study design, collected blood samples prospectively, and had at least 50 cases of the specific cancer being analyzed. The 15 studies in the consortium were conducted in North America (n=10), Europe (n=4), and Asia (n=1) and include 5061 colorectal cancer cases and 6817 breast cancer cases whose circulating 25(OH)D levels have been measured previously or will be measured (mostly as part of this proposal). We will analyze the primary data from each study so that circulating 25(OH)D levels and confounding variables will be modeled consistently across studies. This will reduce potential sources of between-studies heterogeneity due to different analytic approaches as encountered in the published literature, as well as allow for examination of different categorizations of circulating 25(OH)D levels. We also will be able to evaluate whether associations vary among population subgroups, by other biochemical risk factors, and by tumor subtypes which cannot be evaluated fully in a meta-analysis of the published literature. Further, new data will be generated in seven of the studies which will reduce the influence of publication bias. This proposal takes full advantage of extensive data collected throughout the world, builds upon the expertise and established collaboration of the investigators, and takes advantage of the statistical power of the project. These analyses will provide powerful insights into the relation between vitamin D and breast and colorectal cancer risk. The results have the potential to inform recommendations regarding sun exposure and vitamin D intake requirements, and contribute to the reduction of the burden of cancer. PUBLIC HEALTH RELEVANCE: Confirming whether vitamin D reduces the risk of breast and colorectal cancer, two of the most common cancers in the United States, is critical because current health recommendations typically do not encourage intakes of vitamin D high enough to appreciably influence 25(OH)D levels and they tend to discourage sun exposure because of the risk of skin cancer and melanoma.