BackgroundAmong the different tobacco products that are available on the US market, cigarette smoking is shown to be the most harmful and the effects of cigarette smoking have been well studied. US epidemiological studies indicate that non-combustible tobacco products are less harmful than smoking and yet very limited biological and mechanistic information is available on the effects of these alternative tobacco products. For the first time, we characterized gene expression profiling in PBMCs from moist snuff consumers (MSC), compared with that from consumers of cigarettes (SMK) and non-tobacco consumers (NTC).ResultsMicroarray analysis identified 100 differentially expressed genes (DEGs) between the SMK and NTC groups and 46 DEGs between SMK and MSC groups. However, we found no significant differences in gene expression between MSC and NTC. Both hierarchical clustering and principle component analysis revealed that MSC and NTC expression profiles were more similar than to SMK. Random forest classification identified a subset of DEGs which predicted SMK from either NTC or MSC with high accuracy (AUC 0.98).ConclusionsPMBC gene expression profiles of NTC and MSC are similar to each other, while SMK exhibit distinct profiles with alterations in immune related pathways. In addition to discovering several biomarkers, these studies support further understanding of the biological effects of different tobacco products.Trial registrationClinicalTrials.gov. Identifier: NCT01923402. Date of Registration: August 14, 2013. Study was retrospectively registered.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3565-1) contains supplementary material, which is available to authorized users.
To investigate whether cadmium has an independent role in diseases associated with tobacco consumption, epidemiology data were reviewed, biomonitoring data were analyzed, and probabilistic risk assessment (PRA) was performed. Results from previous epidemiology studies have indicated that there are adverse health effects potentially in common between cadmium exposure and tobacco consumption. Analysis of publically available biomonitoring data showed that blood (B-Cd) and urine (U-Cd) cadmium were higher in cigarette smokers compared with smokeless tobacco (SLT) consumers, and B-Cd and U-Cd in SLT consumers were not significantly different than in non-consumers of tobacco. Comparison with previously established biomonitoring equivalent (BE) values indicated that B-Cd and U-Cd in the majority of these cigarette smokers and SLT consumers did not exceed the blood and urine BEs. Results of the PRA showed that the mean hazard estimate was below a generally accepted regulatory threshold for SLT consumers, but not for cigarette smokers. In total, this evaluation indicated that cadmium exposures in tobacco consumers differed by product category consumed; cadmium in tobacco may not be associated with tobacco consumption related diseases; if cadmium in tobacco contributes to tobacco consumption related diseases, differences in hazard and/or risk may exist by product category.
Quantitative risk assessment (QRA), a scientific, evidence-based analytical process that combines chemical and biological data to quantify the probability and potential impact of some defined risk, is used by regulatory agencies for decision-making. Thus, in tobacco product regulation, specifically in substantial equivalence (SE) evaluations, QRA can provide a useful, practical, and efficient approach to address questions that might arise regarding human health risk and potential influence on public health. In SE reporting, when differences in product characteristics may necessitate the determination of whether a new product raises different questions of public health, the results from QRA are a valuable metric. An approach for QRA in this context is discussed, which is modeled after the methodology for assessment of constituent mixtures by the US Environmental Protection Agency for environmental Superfund site assessment. Given the intent in both cases is an assessment of the public health impact resulting from the totality of exposure to a mixture of constituents, the application is appropriate. Although some uncertainties in the information incorporated may exist, relying on the most appropriate of the available data increases the confidence and decreases the uncertainty in the risk characterization using this data-driven methodology.
There are no large-scale, carefully designed cohort studies that provide evidence on whether menthol cigarette use is associated with a differential risk of initiating and/or progressing to increased smoking. However, questions of whether current menthol cigarette smokers initiated smoking at a younger age or are more likely to have transitioned from non-daily to daily cigarette use compared to non-menthol smokers can be addressed using cross-sectional data from U.S. government surveys. Analyses of nationally representative samples of adult and youth smokers indicate that current menthol cigarette use is not associated with an earlier age of having initiated smoking or greater likelihood of being a daily versus non-daily smoker. Some surveys likewise provide information on cigarette type preference (menthol versus non-menthol) among youth at different stages or trajectories of smoking, based on number of days smoked during the past month and/or cigarettes smoked per day. Prevalence of menthol cigarette use does not appear to differ among new, less experienced youth smokers compared to established youth smokers. While there are limitations with regard to inferences that can be drawn from cross-sectional analyses, these data do not suggest any adverse effects for menthol cigarettes on measures of initiation and progression to increased smoking.
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