Interaction of Vitamin D & Vitamin A with Lung Cancer Risk in Non-Smoking Females

维生素 D 的相互作用

基本信息

批准号：
8601154
负责人：
Marian L Neuhouser
金额：
$ 8.54万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-01 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8601154
关键词：
25-hydroxyvitamin D All-Trans-Retinol Area Attenuated Biological Markers Blood Circulation Carotene Cell Nucleus Cells Cervix Uteri Cessation of life Colorectal Cancer Confidence Intervals Data Development Diagnostic Diet Dose Environment Epithelial Esters Exposure to Fasting Female Food Interactions Genetic Transcription Goals Guidelines Health High Pressure Liquid Chromatography High Prevalence Immunoassay Incidence Intake Ligands Literature Logistic Regressions Low Prevalence Lung Malignant neoplasm of lung Malignant neoplasm of prostate Measures Modeling Modification Multivitamin Nested Case-Control Study Nutrient Nutritional Odds Ratio Pancreas Population Study Postmenopause Prevention Research Prevention program Process Prostate RXR Receptor Gene Research Residual state Risk Risk Factors Role Sample Size Sampling Studies Seasons Serum Signal Transduction Smoking Structure Testing Tissues Vitamin A Vitamin D Vitamin D Deficiency Vitamin D3 Receptor Vitamins Woman Women&apos s Health alitretinoin cancer prevention cancer risk carcinogenesis cigarette smoking clinically relevant density detector dietary supplements lung cancer prevention malignant breast neoplasm men mortality never smoker non-smoker non-smoking public health relevance smoking prevalence

项目摘要

DESCRIPTION (provided by applicant): Project Summary Vitamin D is a promising nutritional cancer prevention agent, but most of the relevant research has been conducted on breast, colorectal and prostate cancer. Less is known about the association of vitamin D with lung cancer risk. A major challenge of lung cancer prevention research is that smoking remains the strongest risk factor and has the potential for residual confounding in analyses that examine diet and other exposures. The Women's Health Initiative (WHI) provides an excellent environment in which to examine lung cancer risk factors other than smoking since smoking prevalence was low and a large number of the lung cancer cases are among never smokers. Therefore, our primary objective is to determine the association of vitamin D status with lung cancer risk in never-smoking, postmenopausal women in the WHI. In a nested case-control study of 300 incident lung cancer cases and 300 controls, we will test whether high vs. low serum concentrations of 25- hydroxyvitamin D [25(OH)D], a biomarker of vitamin D status, are associated with reduced lung cancer risk among never-smoking women. In addition, we hypothesize that vitamin A may modify the association of serum 25(OH)D with lung cancer risk. In nuclei, high concentrations of 9-cis-retinoic acid, an active metabolite of vitamin A and the ligand of retinoid X receptor, impedes the proper function of the vitamin D receptor. Thus, high intake of vitamin A, such as supplemental vitamin A use, likely leads to excessively high 9-cis-retinoic acid concentrations both in the circulation and in cells. Previous literature has not considered this potentially important nutrient-nutrient interaction. From our preliminary data, serum concentrations of 25(OH)D are inversely associated with lung cancer mortality among former and never smokers; the association may be attenuated by excess circulating vitamin A or vitamin A supplement use. Thus, in the secondary aim, we will test whether the reduced lung cancer risks associated with high serum concentrations of 25(OH)D are stronger among women without excess circulating vitamin A compared to those with excess circulating vitamin A. The excess circulating vitamin A is defined as serum retinyl esters e7 ¿g/mL and the ratio of retinyl esters to retinol e0.08. We will use a chemiluminescent immunoassay to measure 25(OH)D and high-performance liquid chromatography with UV detector to measure retinyl esters and retinol in pre-diagnostic sera. Serum 25(OH)D concentrations will be classified by using season-specific quartiles, season-standardized quartiles, and clinically relevant concentrations. Logistic regression will be used to estimate multivariate-adjusted odds ratios and 95% confidence intervals for the associations of serum 25(OH) and lung cancer risk. The interaction of serum 25(OH)D and excess vitamin A on lung cancer risk will also be evaluated in regression models.

描述（由适用提供）：项目摘要维生素D是一种有前途的营养癌症预防剂，但大多数相关研究都是在乳腺癌，有色和前列腺癌上进行的。关于维生素D与肺癌风险的关联知之甚少。肺癌预防研究的主要挑战是，吸烟仍然是强大的危险因素，并且有可能在检查饮食和其他暴露的分析中残留混淆。妇女的健康计划（WHI）提供了一个极好的环境，在该环境中，除了吸烟率较低，大量肺癌病例以外，除吸烟以外的肺癌危险因素以外的其他环境。因此，我们的主要目标是确定在从未吸烟的绝经后妇女中，维生素D状况与肺癌风险的关联。在一项针对300例肺癌病例和300例对照的嵌套病例对照研究中，我们将测试高血清浓度25-羟基维生素D [25（OH）D] [25（OH）D]（维生素D状态的生物标志物）与从未吸烟的女性中肺癌的降低有关。此外，我们假设维生素A可能会改变血清25（OH）D与肺癌风险的关联。在核中，高浓度的9-钙摩酸是一种活性的维生素A的活性代谢产物和类维生素X受体的配体，会阻碍维生素D受体的适当功能。这是维生素A的高摄入量，例如补充维生素A的使用，可能导致循环中和细胞中的9- cis-反毒酸浓度极高。以前的文献尚未考虑这种潜在的重要营养素营养素的相互作用。从我们的初步数据中，血清浓度为25（OH）D与以前的肺癌死亡率相反，而从未吸烟。通过过量循环维生素A或维生素A补充剂的使用可能会减弱该关联。在次要目标中，我们将测试与循环维生素A过多的女性相比，与循环过多的女性相比，与高血清浓度相关的肺癌风险降低是否强大。过量的循环维生素A的过量循环维生素A被定义为血清视网膜基酯E7 e7€g/mL和视网膜含量的比率。我们将使用化学发光免疫测定法测量25（OH）D和使用UV探测器的高性能液相色谱法，以测量诊断前血清中的视黄酯和视黄醇。血清25（OH）D浓度将通过使用特定季节的四分位数，季节标准的四分位数和临床相关的浓度来分类。逻辑回归将用于估计血清25（OH）和肺癌风险关联的多元调整后的优势比和95％的置信区间。血清25（OH）D和多余的维生素A对肺癌风险的相互作用也将在回归模型中评估。