Leisure Sedentary Behavior and Risk of Lung Cancer: A Two-Sample Mendelian Randomization Study and Mediation Analysis

Leisure sedentary behavior, especially television watching, has been previously reported as associated with the risk of lung cancer in observational studies. This study aims to evaluate the causal association with two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms associated with leisure television watching, computer use, and driving were extracted from genome-wide association studies. Summary-level results of lung cancer overall and histological types were obtained from International Lung Cancer Consortium (ILCCO). In univariable MR using inverse-variance-weighted method, we observed causal effects of television watching on lung cancer [OR, 1.89, 95% confidence interval (CI), 1.41, 2.54; p = 2.33 × 10−5], and squamous cell lung cancer (OR, 2.37, 95% CI, 1.58, 3.55; p = 3.02 × 10−5), but not on lung adenocarcinoma (OR, 1.40, 95% CI, 0.94, 2.09; p = 0.100). No causal effects of computer use and driving on lung cancer were observed. Television watching significantly increased the exposure to several common risk factors of lung cancer. The associations of television watching with lung cancer and squamous cell lung cancer were compromised after adjusting for smoking quantity with multivariable MR. Our mediation analyses estimated indirect effects of television watching on lung cancer (beta, 0.31, 95% CI, 0.13, 0.52; p = 6.64 × 10−4) and squamous cell lung cancer (beta, 0.33, 95% CI, 0.14, 0.53, p = 4.76 × 10−4) mediated by smoking quantity. Our findings indicate that television watching is positively correlated with the risk of lung cancer, potentially mediated through affecting smoking quantity.

Little Evidence of Modified Genetic Effect of rs16969968 on Heavy Smoking Based on Age of Onset of Smoking

Introduction Tobacco smoking is the leading cause of preventable death globally. Smoking quantity, measured in cigarettes per day (CPD), is influenced both by the age of onset of regular smoking (AOS) and by genetic factors, including a strong effect of the non-synonymous single nucleotide polymorphism rs16969968. A previous study by Hartz et al. reported an interaction between these two factors, whereby rs16969968 risk allele carriers who started smoking earlier showed increased risk for heavy smoking compared to those who started later. This finding has yet to be replicated in a large, independent sample. Methods We performed a preregistered, direct replication attempt of the rs16969968×AOS interaction on smoking quantity in 128,383 unrelated individuals from the UK Biobank, meta-analyzed across ancestry groups. We fit statistical association models mirroring the original publication as well as formal interaction tests on multiple phenotypic and analytical scales. Results We replicated the main effects of rs16969968 and AOS on CPD but failed to replicate the interaction using previous methods. Nominal significance of the rs16969968×AOS interaction term depended strongly on the scale of analysis and the particular phenotype, as did associations stratified by early/late AOS. No interaction tests passed genome-wide correction (α=5e-8), and all estimated interaction effect sizes were much smaller in magnitude than previous estimates. Conclusions We failed to replicate the strong rs16969968×AOS interaction effect previously reported. If such gene-moderator interactions influence complex traits, they likely depend on scale of measurement, and current biobanks lack the power to detect significant genome-wide associations given the minute effect sizes expected. Implications We failed to replicate the strong rs16969968×AOS interaction effect on smoking quantity previously reported. If such gene-moderator interactions influence complex traits, current biobanks lack the power to detect significant genome-wide associations given the minute effect sizes expected. Furthermore, many potential interaction effects are likely to depend on the scale of measurement employed.

The Impact of Cigarette Excise Tax Increases on Regular Drinking Behavior: Evidence from China

(1) Background: Many studies have shown that increasing taxation on cigarettes does play a role in tobacco control, but few studies have focused on whether increasing cigarette excise taxes significantly affects alcohol consumption. In this article, we aim to examine the effects of China’s 2015 increase in the cigarette excise tax on residents’ regular drinking behavior. (2) Methods: Using survey data from China Family Panel Studies (CFPS), we performed a panel logit regression analysis to model the relationship between the cigarette excise tax and regular drinking behavior. The Propensity Score Matching with Difference-in-Differences (PSM-DID) approach was adopted to determine the extent to which the cigarette excise tax affected residents’ drinking behavior. To test whether the cigarette excise tax could change regular drinking behavior by decreasing daily smoking quantity, we used an interaction term model. (3) Results: China’s 2015 increase in the cigarette excise tax had a significant negative effect on the probability of regular alcohol consumption among smokers, and the cigarette excise tax worked by reducing the average daily smoking of smokers. We also found that the regular drinking behavior of male smokers was more deeply affected by the increased cigarette excise tax than females. (4) Conclusions: Our research results not only give a deeper understanding of the impact of the cigarette excise tax, but also provide an important reference with which to guide future decisions concerning excise taxes imposed on cigarettes.

Little Evidence of Modified Genetic Effect of rs16969968 on Heavy Smoking Based on Age of Onset of Smoking

ABSTRACTImportanceTobacco smoking is the leading cause of preventable death globally. Smoking quantity, measured in cigarettes per day (CPD), is influenced both by the age of onset of regular smoking (AOS) and by genetic factors, including a strong association with the non-synonymous single nucleotide polymorphism rs16969968. A previous study1 reported an interaction between these two factors, whereby individuals carrying the risk allele for rs16969968 who started smoking earlier showed increased risk for heavy smoking compared to those who started later. This finding has yet to be replicated in a large, independent sample.ObjectiveTo directly replicate the previous finding, explore the influence of phenotypic and analysis scale on the results, and to assess statistical power to detect gene-moderator interactions.DesignWe performed a preregistered, direct replication attempt of the rs16969968×AOS interaction on smoking quantity in 116,317 unrelated individuals from the UK Biobank. We fit statistical association models mirroring the original publication as well as formal interaction tests on multiple phenotypic and analytical scales.SettingWe used self-report smoking behavior data from the UK Biobank.Participants116,317 unrelated individuals of European ancestry with reported smoking.Exposuresrs16969968 genotype (0, 1 or 2 risk alleles), and AOS, encoded as untransformed, binned, and binary early/late.Main Outcome and MeasuresSelf-reported CPD measured untransformed, log10-transformed, binned and binary heavy/light smoking variables.ResultsWe replicated the main effects of rs16969968 and AOS on CPD. We failed to replicate the interaction using previous methods. Nominal significance of the rs16969968×AOS interaction term depended strongly on the scales of the analysis and the phenotypes, as did associations stratified by early/late AOS. In no analysis did the interaction tests pass genome-wide correction (α=5e-8), and in all analyses, the estimated interaction effect size was smaller in magnitude than previous estimates.Conclusions and RelevanceWe failed to replicate the strong rs16969968×AOS interaction effect on smoking quantity previously reported. If such gene-moderator interactions influence complex traits, current biobanks lack the power to detect significant genome-wide associations given the minute effect sizes expected. Furthermore, many potential interaction effects are likely to depend on the scale of measurement employed.KEY POINTSQuestionDoes the age of regular smoking initiation modify the effect of rs16969968, the strongest smoking-related association, as previously reported?FindingsLimited support for an age of smoking×rs16969968 interaction. Our replication attempt of previous work failed. We found nominally (none genome-wide) significant differences in allele effect sizes, and only with certain combinations of phenotype scales, contrasting previous findings.MeaningIndividual interactions at specific loci are likely very small, and detection will require biobanks many-fold larger than current samples. Furthermore, measurement and analysis scales can strongly impact whether or not an interaction is detected and resulting conclusions.

Polytobacco use among young adult smokers: prospective association with cigarette consumption

Background. The risks of polytobacco use among young adults are unclear because we know relatively little about the consistency of multiproduct patterns over time and how these patterns impact cigarette smoking. The purpose of this study was to examine changes in multiple tobacco product use over time and associations with cigarette smoking quantity.Methods. Participants (n=335; 55% male) were 18–24 years old non-daily cigarette smokers living in California. Polytobacco use patterns were assessed quarterly for 2 years.Results. Transition analyses showed that while the number of products that had been used recently was volatile, the most common pattern was stability between timepoints. A longitudinal negative binomial regression model indicated that those who used more non-cigarette products also reported greater cigarette quantity. The strength of this relationship increased over time.Conclusions. Findings suggest that individuals who use more tobacco products are at greater risk for increased cigarette smoking and maintaining a multiple product use pattern.