Development of biomarkers of exposure and effects for electronic cigarette vs. combustible cigarette use

电子烟与可燃香烟使用的暴露和影响的生物标志物的开发

• 批准号: 10368699
• 负责人: AHMAD BESARATINIA
• 金额: $ 24.75万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368699
• 关键词: Address; Adolescent; Adult; Age; Biological; Biological Assay; Biological Markers; Biological Specimen Banks; Blood Cells; California; Carcinogens; Cardiovascular Diseases; Cardiovascular system; Cells; Characteristics; Chemicals; Cigarette; Collaborations; Collection; Communities; Computer Models; DNA Methylation; Data; Data Analyses; Devices; Disease; Dose; Electronic cigarette; Epigenetic Process; Exposure to; Frequencies; Funding; Genes; Genetic; Genetic Transcription; Genomic DNA; Goals; Health; Immune; Immunity; Inflammation; Inflammatory; Laboratories; Leukocytes; Link; Lung diseases; Malignant Neoplasms; Measures; Methylation; Modeling; Modification; Molecular; Mutation; National Institute of Dental and Craniofacial Research; Nicotine; Oncogene Deregulation; Ontology; Oral; Pathway interactions; Pattern; Population; Public Health; Race; Risk; Sensitivity and Specificity; Smoker; Smoking; Specimen; Study Subject; Tissues; Tobacco; Tobacco use; authority; base; biomarker development; cell type; cigarette smoke; cigarette smoking; combustible cigarette; disorder risk; e-cigarette aerosols; electronic cigarette use; electronic cigarette user; electronic liquid; multiple omics; never smoker; next generation sequencing; non-cigarette tobacco product; non-smoker; novel marker; public health relevance; public repository; recruit; respiratory; sex; smoking cessation; tobacco products; tobacco regulation; toxicant; transcriptome; transcriptome sequencing; transcriptomics; vaper; vaping; variant detection

While the reduced levels of toxicants and carcinogens in electronic cigarette (e-cig) vapor may imply lower health risk, it cannot, however, equate to no risk. In fact, exposure to many of the same constituents of e-cig vapor, at various concentrations, has been associated with a variety of respiratory-, cardiovascular-, and immune-related (inflammatory) diseases, and cancer. To date, the long-term health consequences of vaping are largely unknown. Rationale: The biological effects of many harmful chemicals present in both e-cig vapor and cigarette smoke are ascribed to their ability to induce genetic/epigenetic changes that cause transcriptional deregulation of disease-related genes. Approach: We will perform a multi-omics analysis to detect genetic/epigenetic alterations associated with transcriptional deregulation of key functional genes in oral cells and blood leukocytes of healthy adult vapers and smokers in comparison to controls (nonsmokers non-vapers) (N=45/group, matched for age, sex, and race). Aim 1: Applying RNA-sequencing and gene ontology analysis, “we will first screen for deregulation of disease-related genes in oral- and blood cells of vapers and smokers as compared to controls”. Having identified the deregulated genes in each group, we will then employ targeted next-generation sequencing “to detect genetic changes in Aim 2, and epigenetic modifications in Aim 3 within the deregulated genes”. Integration analysis of data from Aims 2 and 3 will identify loci with detectable genetic/epigenetic changes that differentiate, with the highest sensitivity and specificity, vapers and smokers from controls and from one another. Detectable genetic/epigenetic changes associated with aberrant expression of disease-related genes in cells from vapers vs. smokers can serve as novel biomarkers of exposure and effects for vaping vs. smoking. These biomarkers will help inform the health risks or potential benefits of e-cig use vs. smoking. As a secondary goal, we will perform computational modeling “to find correlations between the identified biomarkers and subjects’ tobacco product use frequency and patterns and product characteristics”. This will inform the impact of vaping/smoking dose and product characteristics, including e-cig device features (e.g., model & power) and e- liquid content (nicotine and flavor), and cigarette brand, type, and chemical constituents (e.g., tar), on the biological effects of e-cig use vs. cigarette smoking. Responsiveness to RFA: This proposal will maximize the use of existing biospecimens from our recently completed NIDCR-funded project whose study subjects were recruited through collaboration with USC-TCORS, which is sponsored by the FDA-CTP. This is a unique collection of biospecimens from a representative population in California. No publicly available repository in the US offers similar specimens required for this project. The specimens are currently stored in the PI’s laboratory, and readily available for use. Impact: The findings of this project may generalize to the broader population of vapers and smokers in the US and across the world, thus being of immediate use for the scientific community and regulatory authorities, and of great relevance to the public’s health.

而电子烟蒸汽中有毒物质和致癌物含量的降低可能意味着健康状况的下降