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

维生素 D 的相互作用

• 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
• 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' 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

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。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) 为检查吸烟以外的肺癌危险因素提供了良好的环境，因为吸烟率较低，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。在一项针对 300 例肺癌病例和 300 例对照的巢式病例对照研究中，我们将测试高血清浓度与低血清浓度 25-羟基维生素 D [25(OH)D]（维生素 D 状态的生物标志物）是否与从不吸烟女性降低肺癌风险相关。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。在细胞核中，高浓度的 9-顺式视黄酸（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）可能会导致循环系统和细胞中的 9-顺式视黄酸浓度过高。以前的文献没有考虑这种潜在重要的营养物质之间的相互作用。根据我们的初步数据，25(OH)D 的血清浓度与曾经吸烟者和从不吸烟者的肺癌死亡率呈负相关。过量循环维生素 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，我们将测试与循环维生素 A 过量的女性相比，与循环维生素 A 过量的女性相比，与高血清浓度 25(OH)D 相关的肺癌风险降低是否更强。循环维生素 A 过量的定义为血清视黄酯 e7 ¿g/mL 以及视黄酯与视黄醇 e0.08 的比率。我们将使用化学发光免疫分析法测量 25(OH)D，并使用带有紫外检测器的高效液相色谱法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四分位数、季节标准化四分位数和临床相关浓度进行分类。物流 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在回归模型中进行评估。