Are Smokers Switching to Vaping at Lower Risk for Cancer? (Electronic Cigarettes and Cancer Risk)

Study Overview
=================
Brief Summary
-----------------
This project will address a growing public health concern, namely, the health risks or benefits of e-cig use relative to cigarette smoking. The investigators will use biomarkers of early effects of relevance to cancer to determine the carcinogenic potential of e-cig use relative to cigarette smoking in oral epithelium, which is a target tissue for smoking-associated cancer. The study population will consist of one group of smokers who are interested in switching to e-cig use (Grp 1), one group of smokers who do not intend to change their smoking habits (Grp 2), and one group of non-users who would like to maintain their nonsmoking non-vaping status (Grp 3); The total number of participants in this project is 150 (n = 50, each group). The investigators will use an integrative 'multi-omics' approach complemented with single-locus/gene validation analyses to detect temporal changes in the genome, epigenome, and transcriptome relevant to cancer in the oral cells of the participants as the intervention progresses.

Detailed Description
-----------------
Electronic cigarettes (e-cig) are increasingly popular among adult smokers and adolescent never smokers. Chemical analyses of e-cig vapor and liquid have shown the presence of many of the same carcinogens as those found in cigarette smoke, albeit in generally lower concentrations. However, the carcinogenic potential of e-cig has not been investigated in e-cig users (otherwise known as 'vapers'). The investigators will investigate the cancer-causing potential of e-cig use as compared to cigarette smoking by quantifying molecular changes linked to risk of cancer in smokers who switch to e-cig use vs. those who maintain their smoking habits. Leveraging a source population for ongoing studies on e-cig, the investigators will recruit smokers who are interested in switching to e-cig use, and two control groups of non-vapers, including smokers and nonsmokers who do not intend to change their smoking and nonsmoking status, respectively (n = 50, each group). Smokers consenting to switch completely to e-cig will be assigned to a 3-month intervention with a standard e-cig with fully described product characteristics. Control groups will maintain their smoking/nonsmoking habits during the intervention. At weekly intervals, the investigators will verify participants' compliance through personal interviews, CO breath tests, cotinine quantification, and vaping/smoking topography measurements. The investigators will use a non-invasive brushing technique to collect oral cells from the inside of the cheeks of all participants at baseline and every 2 weeks, afterwards. The investigators will use an integrative 'multi-omics' approach complemented with single-locus/gene validation analyses to detect temporal changes in the genome, epigenome, and transcriptome relevant to cancer in the oral cells of the participants as the intervention progresses.

Official Title
-----------------
Are Smokers Switching to Vaping at Lower Risk for Cancer?

Conditions
-----------------
Cigarette Smoking

Intervention / Treatment
-----------------
* Device: NIDA Standard Research E-cigarette (SREC)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Being male or female between the ages of 22-55; Being able to read and write in English and understand and give informed consent; Giving consent to strictly follow the study protocol throughout the study; Not planning to move, take an extended vacation, or undergo surgery during the study; Reporting smoking of > 5 manufactured cigarettes per day for at least 1 year (applicable to participants who will undergo intervention with e-cig (Grp 1) or continue to smoke (Grp 2) only); and Presenting with an expired air CO measurement of > 7 parts per million (ppm) at baseline (applicable to participants who will undergo intervention with e-cig (Grp 1) or continue to smoke (Grp 2) only). Exclusion Criteria: Having oral infection/inflammation, gum disease, dental decay, immune system disorders, diabetes, respiratory diseases (e.g., asthma), or kidney diseases; Having any unstable or significant medical condition (e.g., symptomatic heart conditions) in the past 12 months ; Having body mass index < 18 kg/m2 or > 40 kg/m2 Being pregnant or having a baby in the past 12 months; Having uncontrolled mental illness or substance abuse (e.g., alcoholism) or inpatient treatment for those conditions in the past 12 months; Having used recreational or illicit drugs in the past 3 months; Having used any medication known to induce/inhibit CYP450 2A6 enzyme; Having any known allergy to propylene glycol/vegetable glycerin (applicable participants who will undergo intervention with e-cig (Grp 1) only); and Having another member of household participating in the study.

Ages Eligible for Study
-----------------
Minimum Age: 22 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vapers<br>Smokers will switch to NIDA Standard Research E-cigarette (SREC). | Device: NIDA Standard Research E-cigarette (SREC)<br>* Smokers will switch to NIDA Standard Research E-cigarette (SREC).<br>|
| No Intervention: Smokers<br>Smokers will continue to smoke. | |
| No Intervention: Nonsmokers non-vapers<br>Control nonsmokers non-vapers will continue to refrain from smoking or vaping. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic changes | Number and location of DNA damage | 3 months | 
| Epigenetic changes | Number of epigenetic marks | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene expression | Relative gene expression | Every 2 weeks for 3 months | 
| DNA methylation | Pattern and distribution of aberrant DNA methylation | Every 2 weeks for 3 months | 
| Histone modifications | Pattern and distribution of histone marks | Every 2 weeks for 3 months | 
| Mutation | Frequency and location of mutations | Every 2 weeks for 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Electronic Nicotine Delivery System