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，对循环中的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的综合分析。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，在更瘦的人、更多的体力活动的人和钙摄入量更高的人中，这些联系更强。参加该联盟的纳入标准是，一项研究使用了前瞻性研究设计，前瞻性地采集了血液样本，并对至少50例特定癌症进行了分析。该联盟的15项研究是在北美(n=10)、欧洲(n=4)和亚洲(n=1)进行的，其中包括5061例结直肠癌病例和6817例乳腺癌病例，他们的循环25(OH)D水平以前已经或将被测量(主要作为这项建议的一部分)。我们将分析每项研究的主要数据，这样循环中的25(OH)D水平和混杂变量将在研究中得到一致的建模。这将减少因已发表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，并允许检查循环中25(OH)D水平的不同分类。我们还将能够评估相关性是否在人群亚组、其他生化风险因素和肿瘤亚型之间存在差异，这在已发表的文献的荟萃分析中是不能完全评估的。此外，将在其中七项研究中产生新的数据，这将减少发表偏见的影响。该提案充分利用了在世界各地收集的大量数据，建立在调查人员的专门知识和既定合作的基础上，并利用了该项目的统计能力。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强有力的见解。这一结果有可能为有关阳光暴露和维生素D摄入量要求的建议提供参考，并有助于减轻癌症的负担。 与公共健康相关：确认维生素D是否可以降低乳腺癌和结直肠癌的风险是至关重要的，因为目前的健康建议通常不鼓励摄入足够高的维生素D来显著影响25(OH)D的水平，而且由于皮肤癌和黑色素瘤的风险，它们往往会阻止阳光照射。

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.