Beyond Cigarettes Per Day. A Genome-Wide Association Study of the Biomarker Carbon Monoxide

Abstract

Rationale: The CHRNA5-CHRNA3-CHRNB4 locus is associated with self-reported smoking behavior and also harbors the strongest genetic associations with chronic obstructive pulmonary disease (COPD) and lung cancer. Because the associations with lung disease remain after adjustment for self-reported smoking behaviors, it has been asserted that CHRNA5-CHRNA3-CHRNB4 variants increase COPD and lung cancer susceptibility independently of their effects on smoking.Objectives: To compare the genetic associations of exhaled carbon monoxide (CO), a biomarker of current cigarette exposure, with self-reported smoking behaviors.Methods: A total of 1,521 European American and 247 African American current smokers recruited into smoking cessation studies were assessed for CO at intake before smoking cessation. DNA samples were genotyped using the Illumina Omni2.5 microarray. Genetic associations with CO and smoking behaviors (cigarettes smoked per day, Fagerstrom test for nicotine dependence) were studied. Measurements and Main Results:Variants in the CHRNA5-CHRNA3-CHRNB4 locus, including rs16969968, a nonsynonymous variant in CHRNA5, are genomewide association study-significantly associated with CO (b = 2.66; 95% confidence interval [CI], 1.74-3.58; P = 1.65 3 10 28 ), and this association remains strong after adjusting for smoking behavior (b = 2.18; 95% CI, 1.32-3.04; P = 7.47 3 10 27 ). The correlation between CO and cigarettes per day is statistically significantly lower (z = 3.43; P = 6.07 3 10 24 ) in African Americans (r = 0.14; 95% CI, 0.02-0.26; P = 0.003) than in European-Americans (r = 0.36; 95% CI, 0.31-0.40; P = 0.0001).Conclusions: Exhaled CO, a biomarker that is simple to measure, captures aspects of cigarette smoke exposure in current smokers beyond the number of cigarettes smoked per day. Behavioral measures of smoking are therefore insufficient indices of cigarette smoke exposure, suggesting that genetic associations with COPD or lung cancer that persist after adjusting for self-reported smoking behavior may still reflect genetic effects on smoking exposure.

The Effect of Different Case Definitions of Current Smoking on the Discovery of Smoking-Related Blood Gene Expression Signatures in Chronic Obstructive Pulmonary Disease

“…A genome-wide association study of genetic variation underlying eCO levels while adjusting for self report arrived at a similar conclusion where eCO was found to capture aspects of cigarette smoke exposure in current smokers beyond the number of cigarettes smoked per day. 50 Thus for future -omics and other studies, our data strongly suggest the need to complement self-report with an objective measure of active smoking such as eCO to more accurately capture the effects of smoking in these studies.…”

Clinical and radiographic peri‐implant parameters and proinflammatory cytokine levels among cigarette smokers, smokeless tobacco users, and nontobacco users

“…18,19 Moreover, research indicates that nicotine in tobacco upregulates the secretion of proinflammatory cytokines (such as IL-1b and MMP-9), which play a key role in alveolar bone deterioration around natural teeth. 20,21 Increased expression of these proinflammatory cytokines have also been detected in the PISF of patients with peri-implantitis.…”

Which measures of cigarette dependence are predictors of smoking cessation during pregnancy? Analysis of data from a randomized controlled trial

“…35 and weekly smoking urges 36. The FTCD (scored 0–10) consists of six items: number of cigarettes smoked per day 10 or less = 0, 11–20 = 1, 21–30 = 2, 31 or more = 3; time to first cigarette of the day (60+ minutes = 0, 31–60 minutes = 1, 6–30 minutes = 2, 0–5 minutes = 3); difficulty not smoking in no‐smoking areas (no = 0, yes = 1); which cigarette would the smoker most hate to give up scored (‘first of the morning’ = 1, others = 0); smoke more frequently in first hours after waking (no = 0, yes = 1); and smoke when ill in bed (no = 0, yes = 1).…”

“…As a demonstration of predictive validity, we expect that higher scores of these measures would be associated inversely with cessation. The most widely used measure of cigarette dependence is the FTCD 30, 31, 32, 33, while the biochemical marker of expired carbon monoxide (CO) 34, 35 and urge to smoke 36, 37 are also used commonly to measure dependence. The Heaviness of Smoking Index HSI 38, composed of two items from the FTCD (time to first cigarette of the day and number of cigarettes usually smoked per day), has been shown to predict failure of quit attempts in non‐pregnant smokers in both population‐based 24, 37 and clinical studies 27, 31, 32, 39.…”