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.