Childhood asthma and household exposures to nitrogen dioxide and fine particles: a triple-crossover randomized intervention trial.

OBJECTIVE: Triple-crossover randomized controlled intervention trial to test whether reduced exposure to household NO2 or fine particles results in reduced symptoms among children with persistent asthma. METHODS: Children (n = 126) aged 5-11 years with persistent asthma living in homes with gas stoves and levels of NO2 15 ppb or greater recruited in Connecticut and Massachusetts (2015-2019) participated in an intervention involving three air cleaners configured for: (1) NO2 reduction: sham particle filtration and real NO2 scrubbing; (2) particle filtration: HEPA filter and sham NO2 scrubbing; (3) control: sham particle filtration and sham NO2 scrubbing. Air cleaners were randomly assigned for 5-week treatment periods using a three-arm crossover design. Outcome was number of asthma symptom-days during final 14 days of treatment. Treatment effects were assessed using repeated measures, linear mixed models. RESULTS: Measured NO2 was lower (by 4 ppb, p < .0001) for NO2-reducing compared to control or particle-reducing treatments. NO2-reducing treatment did not reduce asthma morbidity compared to control. In analysis controlling for measured NO2, there were 1.8 (95% CI -0.3 to 3.9, p = .10) fewer symptom days out of 14 in the particle-reducing treatment compared to control. CONCLUSIONS: It remains unknown if using an air cleaner alone can achieve levels of NO2 reduction large enough to observe reductions in asthma symptoms. We observed that in small, urban homes with gas stoves, modest reductions in asthma symptoms occurred using air cleaners that remove fine particles. An intervention targeting exposures to both NO2 and fine particles is complicated and further research is warranted. REGISTRATION NUMBER: NCT02258893.

Changing patterns of cigarette and ENDS transitions in the USA: a multistate transition analysis of youth and adults in the PATH Study in 2015-2017 vs 2017-2019.

INTRODUCTION: It is unknown how recent changes in the tobacco product marketplace have impacted transitions in cigarette and electronic nicotine delivery system (ENDS) use. METHODS: A multistate transition model was applied to 24 242 adults and 12 067 youth in waves 2-4 (2015-2017) and 28 061 adults and 12 538 youth in waves 4 and 5 (2017-2019) of the Population Assessment of Tobacco and Health Study. Transition rates for initiation, cessation and product transitions were estimated in multivariable models, accounting for gender, age group, race/ethnicity and daily versus non-daily product use. RESULTS: Changes in ENDS initiation/relapse rates depended on age, including among adults. Among youth who had never established tobacco use, the 1-year probability of ENDS initiation increased after 2017 from 1.6% (95% CI 1.4% to 1.8%) to 3.8% (95% CI 3.4% to 4.2%). Persistence of ENDS-only use (ie, 1-year probability of continuing to use ENDS only) increased for youth from 40.7% (95% CI 34.4% to 46.9%) to 65.7% (95% CI 60.5% to 71.1%) and for adults from 57.8% (95% CI 54.4% to 61.3%) to 78.2% (95% CI 76.0% to 80.4%). Persistence of dual use similarly increased for youth from 48.3% (95% CI 37.4% to 59.2%) to 60.9% (95% CI 43.0% to 78.8%) and for adults from 40.1% (95% CI 37.0% to 43.2%) to 63.8% (95% CI 59.6% to 67.6%). Youth and young adults who used both products became more likely to transition to ENDS-only use, but middle-aged and older adults did not. CONCLUSIONS: ENDS-only and dual use became more persistent. Middle-aged and older adults who used both products became less likely to transition to cigarette-only use but not more likely to discontinue cigarettes. Youth and young adults became more likely to transition to ENDS-only use.

Transitions between cigarette, ENDS and dual use in adults in the PATH study (waves 1-4): multistate transition modelling accounting for complex survey design.

INTRODUCTION: Even prior to 2018, electronic nicotine delivery systems (ENDS) began to dramatically change the landscape of tobacco products and product use patterns in the USA. METHODS: Using a Markov multistate transition model accounting for complex survey design, transition rates between never, non-current, cigarette, ENDS and dual use states were estimated for 23 253 adult participants in waves 1-4 (approximately 2013-2017) of the Population Assessment of Tobacco and Health study. We made short-term transition projections and estimated HRs for age, sex, race/ethnicity, education and income. RESULTS: Cigarette use was persistent among adults, with 89.7% (95% CI 89.1% to 90.3%) of exclusive cigarette users and 86.1% (95% CI 84.4% to 87.9%) of dual users remaining cigarette users (either exclusive or dual) after one wave. In contrast, ENDS use was less persistent, with 72.1% (95% CI 69.6% to 74.6%) of exclusive ENDS users and 50.5% (95% CI 47.8% to 53.3%) of dual users remaining ENDS users (with or without cigarettes) after one wave. Exclusive ENDS users were more likely to start cigarette use after one wave than either never users (HR 25.2; 95% CI 20.9 to 30.5) or non-current users (HR 5.0; 95% CI 4.3 to 5.8). Dual users of ENDS and cigarettes were more likely to stop using cigarettes than exclusive cigarette users (HR 1.9; 95% CI 1.6 to 2.3). Transition rates varied among sociodemographic groups. CONCLUSIONS: Multistate transition models are an effective tool for uncovering and characterising longitudinal patterns and determinants of tobacco use from complex survey data. ENDS use among US adults was less persistent than cigarette use prior to 2018.

Smoking patterns based on birth-cohort-specific histories from 1965 to 2013, with projections to 2041.

BACKGROUND: Characterizing smoking patterns over time is essential for evaluating the impact of tobacco control interventions and predicting smoking-related mortality. Beginning with a 1920s birth cohort, smoking histories (i.e., estimates of smoking initiation and cessation, and prevalence of current and former smokers) were generated. DATA: The Ontario sample (n = 238,411) of the 2003 to 2013 cycles of the Canadian Community Health Survey, which is conducted biennially, was used to obtain cross-sectional information on current smoking behaviour. METHODS: Age at smoking initiation and age at smoking cessation were used to construct smoking histories for each respondent, up to the survey date. An age-period-cohort model was generated and used to examine survival differences by smoking status. Using the model, and adjusting for survival differences in smoking status, the prevalence of current, former and never smokers was estimated in cohorts from 1920 to 1985. Smoking initiation, cessation and intensity were then estimated for age-specific distributions of each birth cohort. These rates were projected forward through to 2041. Smoking patterns by highest level of education were generated using education-stratified models. RESULTS: Smoking histories show clear trends over time by sex, cohort and age. If current patterns persist, smoking prevalence is projected to decline to single digits (below 10%) by 2023 for women and 2040 for men. DISCUSSION: Birth-cohort-specific smoking histories can be generated using cross-sectional health surveys. These cohort histories can describe smoking patterns over time and into the future. In turn, these histories can be used in micro-simulation models to evaluate historic or planned tobacco control interventions, and to project smoking prevalence.

CP*Trends: An Online Tool for Comparing Cohort and Period Trends Across Cancer Sites.

Cohort or period components of trends can provide a rationale for new research or point to clues on the effectiveness of control strategies. Graphical display of trends guides models that quantify the experience of a population. In this paper, a method for smoothing rates by single year of age and year is developed and displayed to show the contributions of period and cohort to trends. The magnitude of the contribution of period and/or cohort in a model for trends may be assessed by the percentage of deviance explained and the relative contributions of cohort (C) and period (P) individually, known as the C-P score. The method is illustrated using Surveillance, Epidemiology, and End Results data (1975-2014) on lung and bronchial cancer mortality in females and prostate and colorectal cancer incidence in males. Smoothed age-period and age-cohort rates provide a useful first step in studies of etiology and the impact of disease control without imposing a restrictive model. We found that, in this data set, cohort predominates for female lung and bronchial cancer and period predominates for male prostate cancer. However, the effects change with age for male colorectal cancer incidence, indicating an age shift in relevant exposures. These methods are applied on an interactive website for both incidence and mortality at over 20 cancer sites in the United States.

Risk factors for metachronous bilateral renal cell carcinoma: A surveillance, epidemiology, and end results analysis.

BACKGROUND: Patients treated for renal cell carcinoma (RCC) may be diagnosed with a metachronous, contralateral tumor. We evaluated the risks of contralateral tumor development using the Surveillance, Epidemiology, and End Results database. METHODS: Among RCC patients, we identified those with a metachronous, contralateral RCC diagnosed ≥1 year after primary diagnosis. We performed a competing risks analysis to evaluate associations between clinicopathologic factors and metachronous, bilateral RCC. Cumulative incidence and standardized incidence ratios (SIRs) were calculated. RESULTS: There were 80,403 cases of RCC identified, with a median follow-up of 8.3 years; of these, 1063 (1.3%) developed metachronous, contralateral RCC (median of 6 years after diagnosis). The cumulative incidence at 10, 20, and 30 years of follow-up was 1.5%, 3.1%, and 4.7%, respectively. An increased risk was observed among men (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.20-1.55), blacks (HR, 2.00; 95% CI, 1.71-2.33), and those with papillary histology (HR, 1.72; 95% CI, 1.41-2.10). Risk of metachronous disease decreased with increasing age at primary diagnosis (HR per 1-year increase, 0.97; 95% CI, 0.96-0.97). The SIRs were highest among those diagnosed at a younger age and remained elevated even after extended follow-up (>10 years). CONCLUSIONS: Our findings suggest that the cumulative incidence of metachronous, contralateral RCC may be higher than previously reported. Younger age, black race, papillary histology, and male sex increase the risk of metachronous, contralateral RCC development. The high SIRs seen in all demographic groups may support a rationale for lifelong surveillance, especially in high-risk subgroups with early disease onset.

Smoking and Lung Cancer Mortality in the United States From 2015 to 2065: A Comparative Modeling Approach.

Background: Tobacco control efforts implemented in the United States since the 1960s have led to considerable reductions in smoking and smoking-related diseases, including lung cancer. Objective: To project reductions in tobacco use and lung cancer mortality from 2015 to 2065 due to existing tobacco control efforts. Design: Comparative modeling approach using 4 simulation models of the natural history of lung cancer that explicitly relate temporal smoking patterns to lung cancer rates. Setting: U.S. population, 1964 to 2065. Participants: Adults aged 30 to 84 years. Measurements: Models were developed using U.S. data on smoking (1964 to 2015) and lung cancer mortality (1969 to 2010). Each model projected lung cancer mortality by smoking status under the assumption that current decreases in smoking would continue into the future (status quo trends). Sensitivity analyses examined optimistic and pessimistic scenarios. Results: Under the assumption of continued decreases in smoking, age-adjusted lung cancer mortality was projected to decrease by 79% between 2015 and 2065. Concomitantly, and despite the expected growth, aging, and longer life expectancy of the U.S. population, the annual number of lung cancer deaths was projected to decrease from 135 000 to 50 000 (63% reduction). However, 4.4 million deaths from lung cancer are still projected to occur in the United States from 2015 to 2065, with about 20 million adults aged 30 to 84 years continuing to smoke in 2065. Limitation: Projections assumed no changes to tobacco control efforts in the future and did not explicitly consider the potential effect of lung cancer screening. Conclusion: Tobacco control efforts implemented since the 1960s will continue to reduce lung cancer rates well into the next half-century. Additional prevention and cessation efforts will be required to sustain and expand these gains to further reduce the lung cancer burden in the United States. Primary Funding Source: National Cancer Institute.

A spatiotemporal back-calculation approach to estimate cancer incidence measures.

Incidence rates are an important population-level disease risk measure. Cancer incidence data in the United States, which are collected by disease registries, have been spatiotemporally sparse. Back-calculation methods can yield incidence estimates for a spatial domain by solving a convolution equation that relates mortality to incidence through survival estimates. We propose a novel back-calculation approach that uses spatiotemporal age-period-cohort (APC) modeling to estimate incidence for spatial units within a region. The method is applied to state-specific lung cancer data in the United States for males ages 30 to 84 in years 1975-2004. SEER data are used to model cancer progression from incidence to mortality along three timescales (APC) and across four regions. Using mortality data from National Vital Statistics System, incidence is back-calculated for unique birth cohorts in 49 states. A conditionally autoregressive model with cubic splines for temporal effects is used to smooth back-calculated estimates. Bayesian estimates of model parameters are obtained using integrated nested Laplace approximation. Results show varying time trends in lung cancer risk across states, which may quantify effects of state policies.

Potential deaths averted in USA by replacing cigarettes with e-cigarettes.

INTRODUCTION: US tobacco control policies to reduce cigarette use have been effective, but their impact has been relatively slow. This study considers a strategy of switching cigarette smokers to e-cigarette use ('vaping') in the USA to accelerate tobacco control progress. METHODS: A Status Quo Scenario, developed to project smoking rates and health outcomes in the absence of vaping, is compared with Substitution models, whereby cigarette use is largely replaced by vaping over a 10-year period. We test an Optimistic and a Pessimistic Scenario, differing in terms of the relative harms of e-cigarettes compared with cigarettes and the impact on overall initiation, cessation and switching. Projected mortality outcomes by age and sex under the Status Quo and E-Cigarette Substitution Scenarios are compared from 2016 to 2100 to determine public health impacts. FINDINGS: Compared with the Status Quo, replacement of cigarette by e-cigarette use over a 10-year period yields 6.6 million fewer premature deaths with 86.7 million fewer life years lost in the Optimistic Scenario. Under the Pessimistic Scenario, 1.6 million premature deaths are averted with 20.8 million fewer life years lost. The largest gains are among younger cohorts, with a 0.5 gain in average life expectancy projected for the age 15 years cohort in 2016. CONCLUSIONS: The tobacco control community has been divided regarding the role of e-cigarettes in tobacco control. Our projections show that a strategy of replacing cigarette smoking with vaping would yield substantial life year gains, even under pessimistic assumptions regarding cessation, initiation and relative harm.

The Application of a Decision-Theoretic Model to Estimate the Public Health Impact of Vaporized Nicotine Product Initiation in the United States.

INTRODUCTION: The public health impact of vaporized nicotine products (VNPs) such as e-cigarettes is unknown at this time. VNP uptake may encourage or deflect progression to cigarette smoking in those who would not have otherwise smoked, thereby undermining or accelerating reductions in smoking prevalence seen in recent years. METHODS: The public health impact of VNP use are modeled in terms of how it alters smoking patterns among those who would have otherwise smoked cigarettes and among those who would not have otherwise smoked cigarettes in the absence of VNPs. The model incorporates transitions from trial to established VNP use, transitions to exclusive VNP and dual use, and the effects of cessation at later ages. Public health impact on deaths and life years lost is estimated for a recent birth cohort incorporating evidence-informed parameter estimates. RESULTS: Based on current use patterns and conservative assumptions, we project a reduction of 21% in smoking-attributable deaths and of 20% in life years lost as a result of VNP use by the 1997 US birth cohort compared to a scenario without VNPs. In sensitivity analysis, health gains from VNP use are especially sensitive to VNP risks and VNP use rates among those likely to smoke cigarettes. CONCLUSIONS: Under most plausible scenarios, VNP use generally has a positive public health impact. However, very high VNP use rates could result in net harms. More accurate projections of VNP impacts will require better longitudinal measures of transitions into and out of VNP, cigarette and dual use. IMPLICATIONS: Previous models of VNP use do not incorporate whether youth and young adults initiating VNP would have been likely to have been a smoker in the absence of VNPs. This study provides a decision-theoretic model of VNP use in a young cohort that incorporates tendencies toward smoking and shows that, under most plausible scenarios, VNP use yields public health gains. The model makes explicit the type of surveillance information needed to better estimate the effect of new products and thereby inform public policy.

Spatiotemporal calibration and resolution refinement of output from deterministic models.

Spatiotemporal calibration of output from deterministic models is an increasingly popular tool to more accurately and efficiently estimate the true distribution of spatial and temporal processes. Current calibration techniques have focused on a single source of data on observed measurements of the process of interest that are both temporally and spatially dense. Additionally, these methods often calibrate deterministic models available in grid-cell format with pixel sizes small enough that the centroid of the pixel closely approximates the measurement for other points within the pixel. We develop a modeling strategy that allows us to simultaneously incorporate information from two sources of data on observed measurements of the process (that differ in their spatial and temporal resolutions) to calibrate estimates from a deterministic model available on a regular grid. This method not only improves estimates of the pollutant at the grid centroids but also refines the spatial resolution of the grid data. The modeling strategy is illustrated by calibrating and spatially refining daily estimates of ambient nitrogen dioxide concentration over Connecticut for 1994 from the Community Multiscale Air Quality model (temporally dense grid-cell estimates on a large pixel size) using observations from an epidemiologic study (spatially dense and temporally sparse) and Environmental Protection Agency monitoring stations (temporally dense and spatially sparse). Copyright © 2016 John Wiley & Sons, Ltd.

Comparison of Smoking History Patterns Among African American and White Cohorts in the United States Born 1890 to 1990.

INTRODUCTION: Characterizing smoking history patterns summarizes life course exposure for birth cohorts, essential for evaluating the impact of tobacco control on health. Limited attention has been given to patterns among African Americans. METHODS: Life course smoking histories of African Americans and whites were estimated beginning with the 1890 birth cohort. Estimates of smoking initiation and cessation probabilities, and intensity can be used as a baseline for studying smoking intervention strategies that target smoking exposure. US National Health Interview Surveys conducted from 1965 to 2012 yielded cross-sectional information on current smoking behavior among African Americans and whites. Additional detail for smokers including age at initiation, age at cessation and smoking intensity were available in some surveys and these were used to construct smoking histories for participants up to the date that they were interviewed. Age-period-cohort models with constrained natural splines provided estimates of current, former and never-smoker prevalence in cohorts beginning in 1890. RESULTS: This approach yielded yearly estimates of initiation, cessation and smoking intensity by age for each birth cohort. Smoking initiation probabilities tend to be lower among African Americans compared to whites, and cessation probabilities also were generally lower. Higher initiation leads to higher smoking prevalence among whites in younger ages, but lower cessation leads to higher prevalence at older ages in blacks, when adverse health effects of smoking become most apparent. CONCLUSIONS: These estimates provide a summary that can be used to better understand the effects of changes in smoking behavior following publication of the Surgeon General's Report in 1964. IMPLICATIONS: A novel method of estimating smoking histories was applied to data from the National Health Interview Surveys, which provided an extensive summary of the smoking history in this population following publication of the Surgeon General's Report in 1964. The results suggest that some of the existing disparities in smoking-related disease may be due to the lower cessation rates in African Americans compared to whites. However, the number of cigarettes smoked is also lower among African Americans. Further work is needed to determine mechanisms by which smoking duration and intensity can account for racial disparities in smoking-related diseases.

Disease risk estimation by combining case-control data with aggregated information on the population at risk.

We propose a novel statistical framework by supplementing case-control data with summary statistics on the population at risk for a subset of risk factors. Our approach is to first form two unbiased estimating equations, one based on the case-control data and the other on both the case data and the summary statistics, and then optimally combine them to derive another estimating equation to be used for the estimation. The proposed method is computationally simple and more efficient than standard approaches based on case-control data alone. We also establish asymptotic properties of the resulting estimator, and investigate its finite-sample performance through simulation. As a substantive application, we apply the proposed method to investigate risk factors for endometrial cancer, by using data from a recently completed population-based case-control study and summary statistics from the Behavioral Risk Factor Surveillance System, the Population Estimates Program of the US Census Bureau, and the Connecticut Department of Transportation.

Age-Period-Cohort approaches to back-calculation of cancer incidence rate.

A compartment model for cancer incidence and mortality is developed in which healthy subjects may develop cancer and subsequently die of cancer or another cause. In order to adequately represent the experience of a defined population, it is also necessary to allow for subjects who are diagnosed at death, as well as subjects who migrate and are subsequently lost to follow-up. Expressions are derived for the number of cancer deaths as a function of the number of incidence cases and vice versa, which allows for the use of mortality statistics to obtain estimates of incidence using survival information. In addition, the model can be used to obtain estimates of cancer prevalence, which is useful for health care planning. The method is illustrated using data on lung cancer among males in Connecticut.

Polymorphisms in DNA repair genes, hair dye use, and the risk of non-Hodgkin lymphoma.

PURPOSE: Genetic polymorphisms in DNA repair genes and hair dye use may both have a role in the development of non-Hodgkin lymphoma (NHL). We aimed to examine the interaction between variants in DNA repair genes and hair dye use with risk of NHL in a population-based case-control study of Connecticut women. METHODS: We examined 24 single nucleotide polymorphisms in 16 DNA repair genes among 518 NHL cases and 597 controls and evaluated the associations between hair dye use and risk of overall NHL and common NHL subtypes, stratified by genotype, using unconditional logistic regression. RESULTS: Women who used hair dye before 1980 had a significantly increased risk of NHL, particularly for the follicular lymphoma (FL) subtype, but not for diffuse large B-cell lymphoma. The following genotypes in combination with hair dye use before 1980 were associated with FL risk: BRCA2 rs144848 AC+CC [odds ratio (OR) (95% confidence interval (CI)) 3.28(1.27-8.50)], WRN rs1346044 TT [OR(95% CI) 2.70(1.30-5.65)], XRCC3 rs861539 CT+TT [OR(95% CI) 2.76(1.32-5.77)], XRCC4 rs1805377 GG [OR(95% CI) 2.07(1.10-3.90)] and rs1056503 TT [OR(95% CI) 2.17(1.16-4.07)], ERCC1 rs3212961 CC [OR(95% CI) 1.93(1.00-3.72)], RAD23B rs1805329 CC [OR(95% CI) 2.28(1.12-4.64)], and MGMT rs12917 CC, rs2308321 AA, and rs2308327 AA genotypes [OR(95% CI) 1.96(1.06-3.63), 2.02(1.09-3.75), and 2.23(1.16-4.29), respectively]. In addition, a significant interaction with risk of overall NHL was observed between WRN rs1346044 and hair dye use before 1980 (p(interaction) = 0.032). CONCLUSIONS: Our results indicated that genetic variation in DNA repair genes modifies susceptibility to NHL in relation to hair dye use, particularly for the FL subtype and in women who began using hair dye before 1980. Further studies are needed to confirm these observations.

General, but not abdominal, overweight increases odds of asthma among Norwegian adolescents: the Young-HUNT study.

AIM: The aim of this analysis was to examine the association between asthma and general and abdominal weight status, defined by age- and sex-specific cut-offs for body mass index (BMI) and waist circumference (WC) in adolescents. METHODS: Participants aged 12-19 years in the Young-HUNT (YH) Study (YH1 1995-1997: n = 8222; YH3 2006-2008: n = 7403) completed self-administered questionnaires in school as part of a series of cross-sectional, population-based studies conducted in Nord-Trøndelag, Norway. Weight, height and WC were measured. Adjusted odds ratios (ORs) and 95% Confidence Intervals (CI) for asthma, defined by self-reported physician diagnosis, were calculated. Potential effect modifiers evaluated included sex and pubertal development status (PDS). RESULTS: Asthma was reported by 11.8% of the adolescents in YH1 and 17.0% in YH3. Asthma odds significantly increased for adolescents with general (OR = 1.33; 95%CI: 1.13, 1.56), but not abdominal, overweight and increased for adolescents with general (OR = 1.34; 95%CI: 1.02, 1.75) or abdominal obesity (OR = 1.36; 95%CI: 1.16, 1.60). Underweight had no association with asthma regardless of weight assessment type, and PDS did not meaningfully influence the associations between asthma and weight. CONCLUSION: Overweight and obesity both increased the odds of asthma in 12-19 year-old Norwegians. WC did not add further information to that already provided by BMI to improve our understanding of the association between asthma and weight.

Tobacco control and the reduction in smoking-related premature deaths in the United States, 1964-2012.

IMPORTANCE: January 2014 marks the 50th anniversary of the first surgeon general's report on smoking and health. This seminal document inspired efforts by governments, nongovernmental organizations, and the private sector to reduce the toll of cigarette smoking through reduced initiation and increased cessation. OBJECTIVE: To model reductions in smoking-related mortality associated with implementation of tobacco control since 1964. DESIGN, SETTING, AND PARTICIPANTS: Smoking histories for individual birth cohorts that actually occurred and under likely scenarios had tobacco control never emerged were estimated. National mortality rates and mortality rate ratio estimates from analytical studies of the effect of smoking on mortality yielded death rates by smoking status. Actual smoking-related mortality from 1964 through 2012 was compared with estimated mortality under no tobacco control that included a likely scenario (primary counterfactual) and upper and lower bounds that would capture plausible alternatives. EXPOSURES: National Health Interview Surveys yielded cigarette smoking histories for the US adult population in 1964-2012. MAIN OUTCOMES AND MEASURES: Number of premature deaths avoided and years of life saved were primary outcomes. Change in life expectancy at age 40 years associated with change in cigarette smoking exposure constituted another measure of overall health outcomes. RESULTS: In 1964-2012, an estimated 17.7 million deaths were related to smoking, an estimated 8.0 million (credible range [CR], 7.4-8.3 million, for the lower and upper tobacco control counterfactuals, respectively) fewer premature smoking-related deaths than what would have occurred under the alternatives and thus associated with tobacco control (5.3 million [CR, 4.8-5.5 million] men and 2.7 million [CR, 2.5-2.7 million] women). This resulted in an estimated 157 million years (CR, 139-165 million) of life saved, a mean of 19.6 years for each beneficiary (111 million [CR, 97-117 million] for men, 46 million [CR, 42-48 million] for women). During this time, estimated life expectancy at age 40 years increased 7.8 years for men and 5.4 years for women, of which tobacco control is associated with 2.3 years (CR, 1.8-2.5) (30% [CR, 23%-32%]) of the increase for men and 1.6 years (CR, 1.4-1.7) (29% [CR, 25%-32%]) for women. CONCLUSIONS AND RELEVANCE: Tobacco control was estimated to be associated with avoidance of 8 million premature deaths and an estimated extended mean life span of 19 to 20 years. Although tobacco control represents an important public health achievement, efforts must continue to reduce the effect of smoking on the nation's death toll.

Smoking patterns by birth cohort in Argentina: an age-period-cohort population-based modeling study.

Background: Argentina's smoking rates remain high. We aim to estimate Argentina age-specific histories of smoking initiation, cessation, prevalence, and intensity by birth-cohort to inform policy interventions. Methods: Modeling study. Data from three Argentinian nationally representative surveys conducted from 2004 to 2018 (n = 268,193) were used to generate smoking histories. The Cancer Intervention and Surveillance Modeling (CISNET) Network Lung Working Group age, period, and cohort modeling approach was used to calculate smoking initiation and cessation probabilities, ever and current smoking prevalence, and intensity (cigarettes per day, CPD) by age, sex, and birth cohort from 1950 to 2018. Findings: Ever smoking prevalence increases with age up to 25 and decreases with birth cohorts after 1990. Smoking initiation peaks between 15 and 18 years of age. Among females, initiation probabilities increased until the 1955 cohort, reaching a second peak in 1980-85 cohorts and declining thereafter. Males have higher initiation probabilities than females. Among males, initiation has decreased since the 1950 birth cohort, with a slight increase around the 1985 cohort. Current smoking prevalence has been decreasing since the 1960 birth cohort, except for a peak in 1980-85 cohorts. Cessation increases with age. Mean CPD increases with age and peaks around age 40, appearing flat in females since the 1985 cohort. Interpretation: Recent birth cohorts seem to be experiencing lower rates of initiation, stable rates of quitting and lower current and ever smoking prevalence. The stabilization of cessation probabilities and mean CPD indicate the need to strengthen existing tobacco control measures and advance new ones. Funding: NIH/NCI U01CA253858 grant.

Role of one-carbon metabolizing pathway genes and gene-nutrient interaction in the risk of non-Hodgkin lymphoma.

PURPOSE: Genetic polymorphisms in one-carbon metabolizing pathway genes have been associated with risk of malignant lymphoma. However, the results have been inconsistent. The objectives of this study were to examine the potential relationship between gene-nutrient interactions and the risk of non-Hodgkin lymphoma (NHL). METHODS: We examined 25 polymorphisms in 16 one-carbon metabolism genes for their main effect and gene-nutrient interactions in relation to NHL risk among 518 incident cases and 597 population-based controls of Connecticut women enrolled between 1996 and 2000. RESULTS: A significantly reduced risk of NHL was associated with the homozygous TT genotype in CBS (rs234706, Ex9+33C>T) (OR = 0.51, 95 % CI 0.31-0.84), the homozygous CC genotype in MBD2 (rs603097, -2176C>T) (OR = 0.37, 95 % CI 0.17-0.79), the heterozygote AG genotype in FTHFD (rs1127717, Ex21+31A>G) (OR = 0.73, 95 % CI 0.55-0.98), and a borderline significantly reduced risk of NHL was observed for the homozygous CC genotype in MTRR (rs161870, Ex5+136T>C) (OR = 0.23, 95 % CI 0.05-1.04). The reduced risk of NHL associated with these genotypes was predominately in those with higher dietary vitamin B6 and methionine intakes, as well as with higher dietary folate intake although results were less stable. A borderline significantly increased risk of NHL was also observed for CBS (rs1801181, Ex13+41C>T), FTHFD (rs2305230, Ex10-40G>T), SHMT1 (rs1979277, Ex12+138C>T), and SHMT1 (rs1979276, Ex12+236T>C), and these associations appeared to be contingent on dietary nutrient intakes. CONCLUSION: Our results suggest that variation in several one-carbon metabolizing pathway genes may influence the risk of NHL through gene-nutrient interactions involving dietary nutrient intakes.

Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma: a pooled analysis within the InterLymph consortium.

PURPOSE: Studies of smoking and risk of non-Hodgkin lymphoma (NHL) have yielded inconsistent results, possibly due to subtype heterogeneity and/or genetic variation impacting the metabolism of tobacco-derived carcinogens, including substrates of the N-acetyltransferase enzymes NAT1 and NAT2. METHODS: We conducted a pooled analysis of 5,026 NHL cases and 4,630 controls from seven case-control studies in the international lymphoma epidemiology consortium to examine associations between smoking, variation in the N-acetyltransferase genes NAT1 and NAT2, and risk of NHL subtypes. Smoking data were harmonized across studies, and genetic variants in NAT1 and NAT2 were used to infer acetylation phenotype of the NAT1 and NAT2 enzymes, respectively. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for risk of NHL and subtypes were calculated using joint fixed effects unconditional logistic regression models. RESULTS: Current smoking was associated with a significant 30 % increased risk of follicular lymphoma (n = 1,176) but not NHL overall or other NHL subtypes. The association was similar among NAT2 slow (OR 1.36; 95 % CI 1.07-1.75) and intermediate/rapid (OR 1.27; 95 % CI 0.95-1.69) acetylators (p (interaction) = 0.82) and also did not differ by NAT1*10 allelotype. Neither NAT2 phenotype nor NAT1*10 allelotype was associated with risk of NHL overall or NHL subtypes. CONCLUSION: The current findings provide further evidence for a modest association between current smoking and follicular lymphoma risk and suggest that this association may not be influenced by variation in the N-acetyltransferase enzymes.