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Targeted plasma proteomics identifies a novel, robust association between cornulin and Swedish moist snuff.

ABSTRACT: Lifestyle behaviors are believed to influence the body's inflammatory state. Chronic low-grade inflammation contributes to the development of major non-communicable diseases such as diabetes, cardiovascular disease and cancer. Inflammation may thus be an important link between lifestyle and disease. We evaluated self-reported physical activity, tobacco use and alcohol consumption in relation to plasma levels of 160 validated inflammatory and cancer biomarkers. The study included 138 participants from a population-based cohort, all with repeated sampling of plasma and data ten years apart, allowing consideration of both intra- and inter-individual variation. Of 17 relationships identified, the strongest was an independent, positive association between cornulin (CRNN) and Swedish moist snuff (snus) use. We replicated the finding in a second cohort of 501 individuals, in which a dose-response relationship was also observed. Snus explained approximately one fifth of the variance in CRNN levels in both sample sets (18% and 23%). In conclusion, we identified a novel, independent, dose-dependent association between CRNN and snus use. Further study is warranted, to evaluate the performance of CRNN as a potential snus biomarker. The putative importance of lifestyle behaviors on a wide range of protein biomarkers illustrates the need for more personalized biomarker cut-offs.

SUBMITTER: Sundkvist A

PROVIDER: S-EPMC5797131 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Targeted plasma proteomics identifies a novel, robust association between cornulin and Swedish moist snuff.

Sundkvist Anneli A Myte Robin R Bodén Stina S Enroth Stefan S Gyllensten Ulf U Harlid Sophia S van Guelpen Bethany B

Scientific reports 20180202 1

Lifestyle behaviors are believed to influence the body's inflammatory state. Chronic low-grade inflammation contributes to the development of major non-communicable diseases such as diabetes, cardiovascular disease and cancer. Inflammation may thus be an important link between lifestyle and disease. We evaluated self-reported physical activity, tobacco use and alcohol consumption in relation to plasma levels of 160 validated inflammatory and cancer biomarkers. The study included 138 participants ...[more]

PMID: 29396534

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Project description:BackgroundSmokeless tobacco (ST) products are widely used throughout the world and contribute to morbidity and mortality in users through an increased risk of cancers and oral diseases. Bacterial populations in ST contribute to taste, but their presence can also create carcinogenic, Tobacco-Specific N-nitrosamines (TSNAs). Previous studies of microbial communities in tobacco products lacked chemistry data (e.g. nicotine, TSNAs) to characterize the products and identify associations between carcinogen levels and taxonomic groups. This study uses statistical analysis to identify potential associations between microbial and chemical constituents in moist snuff products.MethodsWe quantitatively analyzed 38 smokeless tobacco products for TSNAs using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and nicotine using gas chromatography with mass spectrometry (GC-MS). Moisture content determinations (by weight loss on drying), and pH measurements were also performed. We used 16S rRNA gene sequencing to characterize the microbial composition, and additionally measured total 16S bacterial counts using a quantitative PCR assay.ResultsOur findings link chemical constituents to their associated bacterial populations. We found core taxonomic groups often varied between manufacturers. When manufacturer and flavor were controlled for as confounding variables, the genus Lactobacillus was found to be positively associated with TSNAs. while the genera Enteractinococcus and Brevibacterium were negatively associated. Three genera (Corynebacterium, Brachybacterium, and Xanthomonas) were found to be negatively associated with nicotine concentrations. Associations were also investigated separately for products from each manufacturer. Products from one manufacturer had a positive association between TSNAs and bacteria in the genus Marinilactibacillus. Additionally, we found that TSNA levels in many products were lower compared with previously published chemical surveys. Finally, we observed consistent results when either relative or absolute abundance data were analyzed, while results from analyses of log-ratio-transformed abundances were divergent.

Project description:Use of smokeless tobacco products (STPs) is associated with oral cavity cancer and other health risks. Comprehensive analysis for chemical composition and toxicity is needed to compare conventional and newer STPs with lower tobacco-specific nitrosamines (TSNAs) yields. Seven conventional and 12 low-TSNA moist snuff products purchased in the U.S., Sweden, and South Africa were analyzed for 18 chemical constituents (International Agency for Research on Cancer classified carcinogens), pH, nicotine, and free nicotine. Chemicals were compared in each product using Wilcoxon rank-sum test and principle component analysis (PCA). Conventional compared to low-TSNA moist snuff products had higher ammonia, benzo[a]pyrene, cadmium, nickel, nicotine, nitrate, and TSNAs and had lower arsenic in dry weight content and per mg nicotine. Lead and chromium were significantly higher in low-TSNA moist snuff products. PCA showed a clear difference for constituents between conventional and low-TSNA moist snuff products. Differences among products were reduced when considered on a per mg nicotine basis. As one way to contextualize differences in constituent levels, probabilistic lifetime cancer risk was estimated for chemicals included in The University of California's carcinogenic potency database (CPDB). Estimated probabilistic cancer risks were 3.77-fold or 3-fold higher in conventional compared to low-TSNA moist snuff products under dry weight or under per mg nicotine content, respectively. In vitro testing for the STPs indicated low level toxicity and no substantial differences. The comprehensive chemical characterization of both conventional and low-TSNA moist snuff products from this study provides a broader assessment of understanding differences in carcinogenic potential of the products. In addition, the high levels and probabilistic cancer risk estimates for certain chemical constituents of smokeless tobacco products will further inform regulatory decision makers and aid them in their efforts to reduce carcinogen exposure in smokeless tobacco products.

Project description:IntroductionTobacco product characteristics convey product attributes to potential users. This study aimed to assess independent contributions of specific e-cigarette and smokeless tobacco product characteristics to adolescents' perceptions about these products.MethodsIn 2019-2020, students (N=1003) attending a convenience sample of 7 high schools in California (USA) were individually randomized to one of two discrete choice experiments, featuring either electronic cigarettes (e-cigarettes) or moist snuff. Participants were presented like-product pairs of randomlygenerated hypothetical tobacco products differing in device type, flavor, vapor cloud, and nicotine amount (for e-cigarettes) or differing in brand, flavor, cut, and price (for moist snuff). Within pairs, participants were asked about which product they were more curious, was more dangerous, would give a greater 'buzz,' and would be easier to use. Conditional logistic regression was used to quantify independent associations of product characteristics to participants' choices.ResultsEach e-cigarette and moist snuff characteristic was independently associated with multiple product perceptions. All non-tobacco flavors were associated with more curiosity and perceived ease-of-use but lower perceived danger. Tank and pod-type e-cigarettes were viewed as easier to use and garnered more curiosity than 'cigalike' or 'drip-mod' devices. Smaller vapor cloud e-cigarettes and lower-price moist snuff were viewed as less dangerous, less buzz-inducing, and easier to use. Product ever users held stronger perceptions than never users about device type (e-cigarettes) and brands (moist snuff), while product naïve participants more strongly associated flavor with danger and buzz.ConclusionsTobacco product characteristics convey product attributes to adolescents that may increase appeal. Restricting specific characteristics, including flavors, could reduce positive perceptions of these products among youth.

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Targeted plasma proteomics identifies a novel, robust association between cornulin and Swedish moist snuff.

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Targeted plasma proteomics identifies a novel, robust association between cornulin and Swedish moist snuff.

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