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The online version of this article (doi:10.1186/s12889-015-2212-5) contains supplementary material, which is available to authorized users.
AWB, RK and HSJ disclose employment at SRI as a financial competing interest. SRI is financing the cost of the article-processing charge. GES declares employment at SRI within the last 5 years as a financial competing interest. MDL declares no competing interests in the data reported in this communication. JWB discloses employment at BioRealm LLC as a financial competing interest. XC declares no competing interests. LM and BZ were previously employed by the tobacco company sponsor of the TES and involved in aspects of the original study execution and analysis.
AWB directed statistical analyses of TES data and laboratory analyses of biospecimens, performed power analyses, proposed the goals of a future analysis consortium, and drafted and revised the manuscript. RK performed univariate analyses of TES data. HSJ performed multivariate modeling and permutation of TES data. GES reviewed TES documents and publications and helped to draft and revise the manuscript. MDL suggested the concept for the manuscript and contributed to the goals of a future analysis consortium. JWB contributed to the goals of a future analysis consortium, provided comments on the manuscript, and performed genome-wide genotyping on TES DNA samples. XC contributed to the goals of a future analysis consortium. LM provided comments on the manuscript and provided background on the TES. BZ made extensive contributions to the manuscript, provided background on the TES, and contributed to the goals of a future analysis consortium. All authors approved submission of the final manuscript.
The Total Exposure Study was a stratified, multi-center, cross-sectional study designed to estimate levels of biomarkers of tobacco-specific and non-specific exposure and of potential harm in U.S. adult current cigarette smokers (≥one manufactured cigarette per day over the last year) and tobacco product non-users (no smoking or use of any nicotine containing products over the last 5 years). The study was designed and sponsored by a tobacco company and implemented by contract research organizations in 2002–2003. Multiple analyses of smoking behavior, demographics, and biomarkers were performed. Study data and banked biospecimens were transferred from the sponsor to the Virginia Tobacco and Health Research Repository in 2010, and then to SRI International in 2012, for independent analysis and dissemination.
We analyzed biomarker distributions overall, and by biospecimen availability, for comparison with existing studies, and to evaluate generalizability to the entire sample. We calculated genome-wide statistical power for a priori hypotheses. We performed clinical chemistries, nucleic acid extractions and genotyping, and report correlation and quality control metrics.
Vital signs, clinical chemistries, and laboratory measures of tobacco specific and non-specific toxicants are available from 3585 current cigarette smokers, and 1077 non-users. Peripheral blood mononuclear cells, red blood cells, plasma and 24-h urine biospecimens are available from 3073 participants (2355 smokers and 719 non-users). In multivariate analysis, participants with banked biospecimens were significantly more likely to self-identify as White, to be older, to have increased total nicotine equivalents per cigarette, decreased serum cotinine, and increased forced vital capacity, compared to participants without. Effect sizes were small (Cohen’s d-values ≤ 0.11). Power for a priori hypotheses was 57 % in non-Hispanic Black (N = 340), and 96 % in non-Hispanic White (N = 1840), smokers. All DNA samples had genotype completion rates ≥97.5 %; 68 % of RNA samples yielded RIN scores ≥6.0.
Total Exposure Study clinical and laboratory assessments and biospecimens comprise a unique resource for cigarette smoke health effects research. The Total Exposure Study Analysis Consortium seeks to perform molecular studies in multiple domains and will share data and analytic results in public repositories and the peer-reviewed literature. Data and banked biospecimens are available for independent or collaborative research.