Polycyclic Aromatic Hydrocarbons, Vitamin D and Breast Cancer

多环芳烃、维生素 D 与乳腺癌

• 批准号: 10322403
• 负责人: Joyce Rhoden
• 金额: $ 3.88万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10322403
• 关键词: Adverse effects; Aftercare; Apoptosis; Aromatic Hydrocarbons; Aromatic Polycyclic Hydrocarbons; Attenuated; Biological Assay; Blood; Blood specimen; Breast; Breast Cancer Risk Factor; Breast Carcinogenesis; Breast Epithelial Cells; Carcinogens; Cell Proliferation; Cells; Complex; Confidence Intervals; Conflict (Psychology); DNA; DNA Adducts; DNA Damage; Development; Diagnosis; Disease; Environmental Exposure; Enzyme-Linked Immunosorbent Assay; Epidemiology; Epigenetic Process; Exposure to; Fellowship; Food; Genes; Genetic; Genetic Polymorphism; Genotype; Geography; Goals; Health; Human; Incidence; Individual; Intervention; Laboratories; Least-Squares Analysis; Lesion; Link; Logistic Models; Logistic Regressions; Lung; Malignant - descriptor; Malignant Neoplasms; Mammary Tumorigenesis; Mammary gland; Measures; Mentors; Meta-Analysis; Metabolism; Methods; Modeling; Mutation; North Carolina; Odds Ratio; Oxidative Stress; Passive Smoking; Plasma; Play; Population Study; Questionnaires; Research; Research Personnel; Resources; Risk; Risk Factors; Risk Reduction; Role; Sampling; Single Nucleotide Polymorphism; Smoke; Source; Structure; Sun Exposure; Tissues; Toxin; Training; Tumor Suppressor Genes; United States; Universities; Variant; Vitamin D; Woman; ambient air pollution; anti-cancer; anticancer activity; breast cancer diagnosis; cancer diagnosis; cigarette smoke; cost; design; dimethylbenzanthracene; disorder risk; doctoral student; epidemiology study; gene environment interaction; genetic predictors; genotoxicity; improved; innovation; intervention cost; malignant breast neoplasm; mammary; neoplastic; population based; pre-doctoral; prevent; protective effect

PROJECT SUMMARY Applicant. This pre-doctoral fellowship (F31) application is designed to promote the training of Joyce Rhoden, a pre-doctoral student in the Department of Epidemiology at the University of North Carolina. Her goal is to become an independent researcher who conducts innovative, translational health research. During the F31 training the applicant will be mentored by her sponsors Drs. Marilie Gammon and Cathrine Hoyo. Significance. Breast cancer is the most commonly diagnosed cancer among women in the United States. Polycyclic aromatic hydrocarbons (PAHs) result from incomplete combustion and are ubiquitous. Many, but not all, studies show positive associations between PAHs and breast cancer risk. Vitamin D significantly protects against oxidative stress in breast epithelial cells and is associated with lower breast cancer risk. Vitamin D prevents pre-neoplastic lesions in mammary gland explants after exposure to the PAH carcinogen 7,12- dimethylbenz(a)-anthracene (DMBA). However, no epidemiologic study has examined if associations between PAHs and breast cancer incidence vary with plasma vitamin D or vitamin D polymorphisms. The study hypothesis is that elevated risks for breast cancer incidence associated with PAHs will be evident only in women with low vitamin D levels, or with genotypes that may lower vitamin D levels. Aim 1. Determine if PAH measures (PAH-DNA adducts and PAH sources (active and passive smoking, grilled/smoked foods, indoor fireplace use, vehicular traffic)) interact with plasma 25-hydroxyvitaminD (25-OHD) concentrations to influence breast cancer risk. Aim 2. Determine if PAH measures interact with any of 25 vitamin D-related genetic single- nucleotide polymorphisms (SNPs) to influence breast cancer incidence. Aim 3. Determine if genetically predicted vitamin D levels influences breast cancer risk and assess whether the genetically predicted vitamin D levels modify the PAH-breast cancer associations. Approach. The dissertation will use existing information from 1508 women with breast cancer and 1556 women without breast cancer. Measures of PAH and vitamin D were assessed shortly after diagnosis. For Aims 1-3, logistic regression will be conducted to estimate odds ratios and 95% confidence intervals to examine interaction on the multiplicative and additive scales. For Aim 3, an adjusted two-stage least squares regression method will be used to estimate a weighted genetic predictive score, which can then be used in logistic models. Innovation. This dissertation: (1) will be the first epidemiologic study to examine interaction between PAHs and vitamin D in association with breast cancer risk; (2) includes multi-level PAH and vitamin D measures; (3) explores biologically plausible SNPs; (4) will estimate genetically predicted vitamin D levels; and (5) uses a well-characterized population-based sample. Impact. The proposed dissertation may identify a potential low-cost risk reduction strategy for breast cancer.

项目摘要 申请人。该博士前奖学金（F31）申请旨在促进乔伊斯·罗登（Joyce Rhoden）的培训， 北卡罗来纳大学流行病学系的博士前学生。她的目标是 成为一名独立研究人员，从事创新的转化健康研究。在F31期间 培训申请人将由她的赞助商Drs指导。 Marilie Gammon和Cathrine Hoyo。 意义。乳腺癌是美国女性中最常见的癌症。 多环芳烃（PAHS）是由不完整的燃烧引起的，并且无处不在。许多，但不是 所有研究表明，PAH与乳腺癌风险之间的正相关。维生素D明显保护 针对乳腺上皮细胞中的氧化应激，与较低的乳腺癌风险有关。维生素d 暴露于PAH致癌7,12- Dimethylbenz（A） - 蒽（DMBA）。但是，没有流行病学研究检查 PAH和乳腺癌的发病率随血浆维生素D或维生素D多态性而变化。研究 假设是，与PAH相关的乳腺癌发病率的升高只有在 维生素D水平低的女性或可能降低维生素D水平的基因型。目标1。确定是否PAH 措施（PAH-DNA加合物和PAH来源（活跃和被动吸烟，烤/烟熏食品，室内 使用壁炉，车辆交通））与等离子体25-羟基维坦丹（25-OHD）浓度相互作用 乳腺癌风险。 AIM 2。确定PAH是否与25个维生素D相关的遗传单相互作用 核苷酸多态性（SNP）影响乳腺癌的发生。目标3。确定是否遗传 预测的维生素D水平会影响乳腺癌的风险，并评估遗传学预测的维生素D 水平改变了PAH乳腺癌的关联。方法。论文将使用现有信息 从1508名乳腺癌妇女和1556名没有乳腺癌的妇女。 PAH和维生素D的度量 诊断后不久评估。对于目标1-3，将进行逻辑回归以估计赔率 比率和95％的置信区间，以检查乘法和添加量表上的相互作用。对于目标3， 调整后的两阶段最小二乘回归方法将用于估计加权遗传预测 得分，然后可以在逻辑模型中使用。创新。本文论文：（1）将是第一个 流行病学研究以检查与乳腺癌风险有关的PAHS与维生素D之间的相互作用； （2）包括多级PAH和维生素D措施； （3）探索生物学上合理的SNP； （4）将估计 遗传预测的维生素D水平； （5）使用良好的基于​​人群的样本。影响。 拟议的论文可能会确定乳腺癌潜在的低成本风险策略。