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：
8443600
负责人：
Marian L Neuhouser
金额：
$ 8.8万
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 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8443600
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（由申请人提供）：项目摘要维生素 D 是一种很有前途的营养性癌症预防剂，但大多数相关研究都是针对乳腺癌、结直肠癌和前列腺癌进行的，但人们对维生素 D 与肺癌风险之间的关系知之甚少。肺癌预防研究的一个主要挑战是吸烟仍然是最强的危险因素，并且在检查饮食和其他暴露的分析中可能会产生残余混杂因素。妇女健康倡议 (WHI) 为检查肺癌风险提供了良好的环境。吸烟以外的因素由于吸烟率较低，而且大量肺癌病例是从不吸烟的人，因此，我们的主要目标是确定 WHI 中从不吸烟的绝经后女性的维生素 D 状况与肺癌风险之间的关系。对 300 例肺癌病例和 300 例对照进行巢式病例对照研究，我们将测试 25-羟基维生素 D [25(OH)D]（维生素 D 状态的生物标志物）的高血清浓度与低血清浓度是否存在差异。此外，我们还发现，维生素 A 可能会改变细胞核中高浓度的 9-顺式视黄酸（9-顺式视黄酸）与肺癌风险的关系。维生素 A 的活性代谢物和类视黄醇 X 受体的配体会阻碍维生素 D 受体的正常功能，因此，大量摄入维生素 A（例如补充维生素 A）可能会导致 9-顺式视黄酸过高。以前的文献并未考虑到这种潜在的重要营养物质之间的相互作用，从我们的初步数据来看，25(OH)D 的血清浓度与吸烟者和从不吸烟者的肺癌死亡率呈负相关。过量的循环维生素 A 或维生素 A 补充剂的使用可能会减弱这种关联，因此，在次要目标中，我们将测试在没有过量循环维生素的女性中，与高血清浓度 25(OH)D 相关的肺癌风险降低是否更大。 A与循环过剩的人相比维生素 A。过量的循环维生素 A 被定义为血清视黄酯 e7 ¿ g/mL 以及视黄酯与视黄醇的比率 e0.08 我们将使用化学发光免疫分析法测量 25(OH)D，并使用带有 UV 检测器的高效液相色谱来测量诊断前血清中的视黄酯和视黄醇。 25(OH)D 浓度将使用季节特定四分位数、季节标准化四分位数和临床相关浓度进行分类。回归将用于估计血清 25(OH) 与肺癌风险关联的多变量调整比值比和 95% 置信区间。血清 25(OH)D 和过量维生素 A 对肺癌风险的相互作用也将被评估。在回归模型中进行评估。