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Background: Reducing cigarettes per day may lower the risk of lung cancer compared with continuing to smoke at the same intensity. Other changes in smoking behaviors, such as increasing cigarette consumption or quitting for a period and relapsing, may also affect lung cancer risk., Methods: We examined changes in smoking status and cigarettes per day among 24 613 Finnish male smokers aged 50-69 years who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Longitudinal data on smoking were collected during study follow-up visits 3 times a year (approximately every 4 months) between 1985 and 1993. Incident lung cancer patients through 2012 were identified by the Finnish Cancer Registry. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression., Results: Compared with smoking 20 cigarettes per day continuously across the intervention period, reducing an average of 5 cigarettes per day per year while smoking was associated with a 20% lower risk of lung cancer (95% CI = 0.71 to 0.90). A substantially lower risk of lung cancer was also observed when participants smoked at 50% (RR = 0.72, 95% CI = 0.57 to 0.90) and 10% (RR = 0.55, 95% CI = 0.36 to 0.83) of study visits, relative to smoked at 100% of study visits., Conclusions: Smokers may lower their risk of lung cancer by reducing smoking intensity (cigarettes per day while smoking) and the time they smoke. However, quitting smoking completely is the most effective way for smokers to reduce their risk of lung cancer., (Published by Oxford University Press 2024.)

Background: In the United States, lung cancer death rates have been declining for decades, primarily as a result of pronounced decreases in cigarette smoking. It is unclear, however, whether there have been similar declines in mortality rates of lung cancer unrelated to smoking. We estimated trends in US lung cancer death rates attributable and not attributable to smoking from 1991 to 2018., Methods: The study included 30- to 79-year-olds in the National Health Interview Survey who were linked to the National Death Index, 1991-2014. Adjusted hazard ratios for smoking status and lung cancer death were estimated, and age-specific population attributable fractions were calculated. Annual population attributable fractions were multiplied by annual US national lung cancer mortality, partitioning rates into smoking-attributable and smoking-unrelated lung cancer deaths. All statistical tests were 2-sided., Results: During 1991-2018, the proportion of never smokers increased among both men (35.1%-54.6%) and women (54.0%-65.4%). Compared with those who had ever smoked, those who had never smoked had 86% lower risk (hazard ratio = 0.14; 95% confidence interval [CI] = 0.12 to 0.16) of lung cancer death. The fraction of lung cancer deaths attributable to smoking decreased from 81.4% (95% CI = 78.9 to 81.4) to 74.7% (95% CI = 78.1 to 71.4). Smoking-attributable lung cancer death rates declined 2.7% per year (95% CI = ‒2.9% to ‒2.5%) and smoking-unrelated lung cancer death rates declined 1.8% per year (95% CI = ‒2.0% to ‒1.5%); these declines have accelerated in recent years., Conclusions: An increasing proportion of lung cancer deaths are unrelated to smoking based on declines in smoking prevalence. Smoking-unrelated lung cancer death rates have declined, however, perhaps because of decreases in secondhand smoke and air pollution exposure as well as treatment improvements., (Published by Oxford University Press 2023.)

Introduction: The impact of cigarette smoking on mortality is well studied, with estimates of the relative mortality risks for the overall population widely available. However, age-specific mortality estimates for different sociodemographic groups in the U.S. are lacking., Methods: Using the 1987-2018 National Health Interview Survey Linked Mortality Files through 2019, all-cause mortality relative risks (RRs) were estimated for current smokers or recent quitters and long-term quitters compared with those for never smokers. Stratified Cox proportional hazards regression models were used to estimate RRs by age, gender, race/ethnicity, and educational attainment. RRs were also assessed for current smokers or recent quitters by smoking intensity and for long-term quitters by years since quitting. The analysis was conducted in 2021-2022., Results: All-cause mortality RRs among current smokers or recent quitters were generally highest for non-Hispanic White individuals than for never smokers, followed by non-Hispanic Black individuals, and were lowest for Hispanic individuals. RRs varied greatly by educational attainment; generally, higher-education groups had greater RRs associated with smoking than lower-education groups. Conversely, the RRs by years since quitting among long-term quitters did not show clear differences across race/ethnicity and education groups. Age-specific RR patterns varied greatly across racial/ethnic and education groups as well as by gender., Conclusions: Age-specific all-cause mortality rates associated with smoking vary considerably by sociodemographic factors. Among high-education groups, lower underlying mortality rates for never smokers result in correspondingly high RR estimates for current smoking. These estimates can be incorporated in modeling analyses to assess tobacco control interventions' impact on smoking-related health disparities between different sociodemographic groups., (Copyright © 2022 American Journal of Preventive Medicine. All rights reserved.)

Introduction: To help target preventive strategies, we estimated US population attributable risks (PARs) of demographic and potentially modifiable risk factors for esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric noncardia adenocarcinoma (GNCA)., Methods: We prospectively examined the associations for risk factors and these cancers in 490,605 people in the National Institutes of Health-the American Association of Retired Persons Diet and Health cohort Diet and Health Study cohort from 1995 to 2011. Exposures were obtained from the baseline questionnaire. Diagnoses of gastroesophageal reflux disease were extracted for a subset of eligible National Institutes of Health-the American Association of Retired Persons Diet and Health cohort subjects through linkage to Medicare and then multiply imputed for non-Medicare-eligible subjects. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards regression. Adjusted population attributable risks were calculated for the US population aged 50-71 years by combining the hazard ratios with the estimated joint distribution of risk factor prevalence from the 2015 National Health Interview Survey., Results: Smoking remained the most important risk factor for ESCC and was estimated to cause more than 1/3 of EAC and GCA and 1/10 of GNCA. Obesity and gastroesophageal reflux disease were associated with more than 1/2 of EAC and 1/3 of GCA. Compared with each lowest-risk level category, common risk factors were estimated to be associated with 73.7% of ESCC (95% confidence interval [CI]: 62.1%-85.4%), 70.3% of EAC (95% CI: 64.4%-76.2%), 69.3% of GCA (95% CI: 61.0%-77.7%), and 33.6% of GNCA (95% CI: 21.7%-45.5%)., Discussion: These factors accounted for a large proportion of esophageal and gastric cancers in the United States, highlighting opportunities for education and intervention to reduce the burden of these highly fatal cancers., (Copyright © 2021 by The American College of Gastroenterology.)

Background: Little is known about the health harms associated with low-intensity smoking in Asians who, on average, smoke fewer cigarettes and start smoking at a later age than their Western counterparts., Methods: In this pooled analysis of 738 013 Asians from 16 prospective cohorts, we quantified the associations of low-intensity (<5 cigarettes/day) and late initiation (≥35 years) of smoking with mortality outcomes. HRs and 95% CIs were estimated for each cohort by Cox regression. Cohort-specific HRs were pooled using random-effects meta-analysis., Findings: During a mean follow-up of 11.3 years, 92 068 deaths were ascertained. Compared with never smokers, current smokers who consumed <5 cigarettes/day or started smoking after age 35 years had a 16%-41% increased risk of all-cause, cardiovascular disease (CVD), respiratory disease mortality and a >twofold risk of lung cancer mortality. Furthermore, current smokers who started smoking after age 35 and smoked <5 cigarettes/day had significantly elevated risks of all-cause (HRs (95% CIs)=1.14 (1.05 to 1.23)), CVD (1.27 (1.08 to 1.49)) and respiratory disease (1.54 (1.17 to 2.01)) mortality. Even smokers who smoked <5 cigarettes/day but quit smoking before the age of 45 years had a 16% elevated risk of all-cause mortality; however, the risk declined further with increasing duration of abstinence., Conclusions: Our study showed that smokers who smoked a small number of cigarettes or started smoking later in life also experienced significantly elevated all-cause and major cause-specific mortality but benefited from cessation. There is no safe way to smoke-not smoking is always the best choice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: An increasing proportion of US smokers smoke at low intensity and not every day. Some nondaily smokers have always had this pattern, whereas others previously smoked daily. The effect of reducing the level of smoking from daily to nondaily smoking and the dose response at low smoking levels are poorly understood., Objective: To evaluate risk of all-cause and cause-specific mortality among nondaily and daily cigarette smokers, by cigarettes per month, years after reducing from daily to nondaily smoking, and years since quitting., Design, Setting, and Participants: A prospective cohort study using harmonized data from multiple cycles of the Tobacco Use Supplements to the Current Population Survey (TUS-CPS), linked to the National Death Index, were analyzed during the period from 2018 to 2020. Adults completed the 1992-1993, 1995-1996, 1998-1999, 2000, 2001-2002, 2003, 2006-2007, or 2010-2011 TUS-CPS. Cigarette smokers were classified as daily or nondaily users; current nondaily smokers were further categorized by whether they previously smoked every day., Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs for risks of mortality vs never smoking. Age was the underlying time metric, adjusted for sex, race/ethnicity, education, survey year, and household income., Results: Among 505 500 participants (aged 18-103 years), approximately 47 000 deaths occurred. The median number of cigarettes smoked per month was 600 (interquartile range, 300-600) (20 cigarettes per day [interquartile range, 10-20 cigarettes per day]) for daily cigarette smokers and 40 (interquartile range, 15-90) for lifelong nondaily smokers. Nevertheless, both current daily (HR, 2.32; 95% CI, 2.25-2.38) and lifelong nondaily (HR, 1.82; 95% CI, 1.65-2.01) smokers had higher all-cause mortality risks than never smokers. Associations were observed for 6 to 10 cigarettes per month and increased with greater-intensity use. Nondaily smokers who previously smoked every day had lower mortality risks than daily smokers, with similar HRs after 10 or more years of nondaily smoking as lifelong nondaily smokers (HR vs never smokers, 1.73; 95% CI, 1.56-1.92). Yet, their risks were higher than former smokers who quit 10 or more years before (HR vs never smokers, 1.18; 95% CI, 1.15-1.22)., Conclusions and Relevance: Although reducing smoking from daily to nondaily was associated with decreased mortality risk, cessation was associated with far greater benefit. Lifelong nondaily smokers have higher mortality risks than never smokers, even among those smoking 6 to 10 cigarettes per month. Thus, all smokers should quit, regardless of how infrequently they smoke.

Background: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease., Methods: We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (≥17 years), two recruited middle-aged and older adults (≥45 years), and two recruited only elderly adults (≥65 years) with examinations done between 1983 and 2014. FEV 1 decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV 1 decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption., Findings: 25 352 participants (ages 17-93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3-20), FEV 1 decline at the median age (57 years) was 31·01 mL per year (95% CI 30·66-31·37) in sustained never-smokers, 34·97 mL per year (34·36-35·57) in former smokers, and 39·92 mL per year (38·92-40·92) in current smokers. With adjustment, former smokers showed an accelerated FEV 1 decline of 1·82 mL per year (95% CI 1·24-2·40) compared to never-smokers, which was approximately 20% of the effect estimate for current smokers (9·21 mL per year; 95% CI 8·35-10·08). Compared to never-smokers, accelerated FEV 1 decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption (<10 pack-years). With respect to current cigarette consumption, the effect estimate for FEV 1 decline in current smokers consuming less than five cigarettes per day (7·65 mL per year; 95% CI 6·21-9·09) was 68% of that in current smokers consuming 30 or more cigarettes per day (11·24 mL per year; 9·86-12·62), and around five times greater than in former smokers (1·57 mL per year; 1·00-2·14). Among participants without prevalent lung disease, associations were attenuated but were consistent with the main results., Interpretation: Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage., Funding: National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear., Methods: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided., Results: Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend < .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers., Conclusions: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract., (Published by Oxford University Press 2019. This work is written by US Government employees and is in the public domain in the United States.)

Background: Previously we showed that adulthood body mass index (BMI) trajectories that result in obesity were associated with elevated risks of fatal prostate cancer (PCA). To further explore this relationship, we conducted a study within the NIH-AARP Diet and Health Study., Methods: Among 153 730 eligible men enrolled in the NIH-AARP cohort from 1995 to 1996 (median follow-up = 15.1 years), we identified 630 fatal PCA cases and 16 896 incident cases. BMI was assessed for ages 18, 35 and 50 and at study entry, enabling examination of latent class-identified BMI trajectories. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression., Results: BMI at study entry (mean age = 63, HR = 1.12; 95% CI = 1.01, 1.24, per 5-unit increase) and maximum BMI during adulthood (HR = 1.12; 95% CI = 1.02, 1.24, per 5-unit increase) shared modest associations with increased risk of fatal PCA. Smoking status likely modified the relationship between BMI trajectories and fatal PCA (Pinteraction = 0.035 via change-in-estimate variable section, P = 0.065 via full a priori model). Among never-smokers, BMI trajectory of normal weight to obesity was associated with increased risk of fatal disease (HR = 2.37; 95% CI = 1.38, 4.09), compared with the maintained normal weight trajectory, whereas there was no association among former or current-smokers. Total and non-aggressive PCA exhibited modest inverse associations with BMI at all ages, whereas no association was observed for aggressive PCA., Conclusions: Increased BMI was positively associated with fatal PCA, especially among never-smokers. Future studies that examine PCA survival will provide additional insight as to whether these associations are the result of biology or confounding., (Published by Oxford University Press on behalf of the International Epidemiological Association 2018. This work is written by US Government employees and is in the public domain in the US.)

Background: How carcinogen exposure varies across users of different, particularly noncigarette, tobacco products remains poorly understood., Methods: We randomly selected 165 participants of the Golestan Cohort Study from northeastern Iran: 60 never users of any tobacco, 35 exclusive cigarette, 40 exclusive (78% daily) waterpipe, and 30 exclusive smokeless tobacco (nass) users. We measured concentrations of 39 biomarkers of exposure in 4 chemical classes in baseline urine samples: tobacco alkaloids, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC). We also quantified the same biomarkers in a second urine sample, obtained 5 years later, among continuing cigarette smokers and never tobacco users., Results: Nass users had the highest concentrations of tobacco alkaloids. All tobacco users had elevated TSNA concentrations, which correlated with nicotine dose. In both cigarette and waterpipe smokers, PAH and VOC biomarkers were higher than never tobacco users and nass users, and highly correlated with nicotine dose. PAH biomarkers of phenanthrene and pyrene and two VOC metabolites (phenylmercapturic acid and phenylglyoxylic acid) were higher in waterpipe smokers than in all other groups. PAH biomarkers among Golestan never tobacco users were comparable to those in U.S. cigarette smokers. All biomarkers had moderate to good correlations over 5 years, particularly in continuing cigarette smokers., Conclusions: We observed two patterns of exposure biomarkers that differentiated the use of the combustible products (cigarettes and waterpipe) from the smokeless product. Environmental exposure from nontobacco sources appeared to contribute to the presence of high levels of PAH metabolites in the Golestan Cohort., Impact: Most of these biomarkers would be useful for exposure assessment in a longitudinal study., (©2019 American Association for Cancer Research.)

Background: While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type., Methods: The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression., Results: Current smokers at baseline had an increased risk of HCC (hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.57-2.20) and ICC (HR = 1.47, 95% CI: 1.07-2.02). Among individuals who quit smoking >30 years ago, HCC risk was almost equivalent to never smokers (HR = 1.09, 95% CI: 0.74-1.61). Compared to non-drinkers, heavy alcohol consumption was associated with an 87% increased HCC risk (HR ≥7 drinks/day  = 1.87, 95% CI: 1.41-2.47) and a 68% increased ICC risk (HR ≥5 drinks/day  = 1.68, 95% CI: 0.99-2.86). However, light-to-moderate alcohol consumption of <3 drinks/day appeared to be inversely associated with HCC risk (HR >0-<0.5 drinks/day  = 0.77, 95% CI: 0.67-0.89; HR >0.5-<1 drinks/day  = 0.57, 95% CI: 0.44-0.73; HR 1-<3 drinks/day  = 0.71, 95% CI: 0.58-0.87), but not ICC., Conclusions: These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC.

Introduction: Use of non-cigarette tobacco products such as cigars and pipe has been increasing, even though these products entail exposure to similar carcinogens to those in cigarettes. More research is needed to explore the risk of these products to guide cancer prevention efforts. Methods: To measure the association between cigars and/or pipe smoking, and cancer incidence in men, we performed meta-analyses of data from five prospective cohorts. Cox regression was used to evaluate the association between different aspects of cigars and pipe smoking and risk of each smoking-related cancer (head and neck, esophagus, lung, stomach, liver, pancreas, kidney, and bladder) for each study. Adjusted HRs were combined using random-effects models. Results: Cigars and/or pipe smokers were at increased risk for head and neck [HR, 1.51; 95% confidence interval (CI), 1.22-1.87], lung (HR, 2.04; 95% CI, 1.68-2.47), and liver cancers (HR, 1.56; 95% CI, 1.08-2.26). Ever-smokers of cigars and/or pipe had an increased risk of developing a smoking-related cancer when compared with never smokers of any tobacco product (overall HR, 1.07; 95% CI, 1.03-1.12). The risk for smoking-related cancers was also increased in mixed smokers who smoked cigars or pipe as well as cigarettes, even when they were smoking predominantly pipe or cigars. Discussion: This pooled analysis highlights the increased risk for smoking-related cancers, particularly for lung and head and neck cancers in exclusive and predominant smokers (former and current) of cigars and pipe. Tobacco prevention efforts should include these products in addition to cigarettes. Cancer Prev Res; 10(12); 704-9. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Introduction: Selecting individuals on the basis of model-predicted risks has been reported to improve lung cancer screening efficiency. On the basis of case-control studies, time to first cigarette (TTFC), a nicotine dependency measurement, has been a strong independent predictor of lung cancer risk. Our objective was to verify the TTFC-lung cancer association in the prospective National Lung Screening Trial and evaluate whether adding TTFC can improve lung cancer risk-prediction models., Methods: Using Cox models, we examined associations between TTFC (≤5, 6-14, 15-29, 30-59, and ≥60 minutes) and lung cancer incidence and death in 18,729 National Lung Screening Trial participants, adjusting for smoking and other lung cancer risk factors comprehensively. We estimated 5-year individual lung cancer incidence by using models without and with TTFC and dichotomized into screening or no-screening groups based on risk thresholds of 1% and 2%. Area under the receiver operating curve values were calculated for models without and with TTFC., Results: Smokers with a TTFC of 60 minutes or more had a much lower standardized 5-year lung cancer incidence risk-1.54% (1.52%-1.56%) for TTFC 60 minutes or more versus 4.07% (4.04%-4.09%) for TTFC 5 minutes or less-and lung cancer death risk-0.59% (0.57%-0.61%) for TTFC 60 minutes or more versus 2.26% (2.23%-2.28%) for TTFC 5 minutes or less (p trend < 0.001). Adding TTFC to the lung cancer incidence model improved the area under the receiver operating curve by 0.0079 (95% confidence interval = 0.0019-0.0138 [p = 0.0085]). Among 8994 smokers without a lung cancer diagnosis, 180 (2.00%) and 155 (1.67%) more people would be assigned to the no-screening group by adding TTFC to the model (p values for percent changes <0.001) at the 1% and 2% risk thresholds, respectively., Conclusion: Including TTFC, which can be elicited by a single question at very low cost and noninvasively question, into risk models might better identify smokers with lower risk and could therefore be a safe, convenient tool to improve identification of those who benefit less from lung cancer screening., (Published by Elsevier Inc.)

Background: There is limited information about the hazards of cigarettes, smokeless tobacco and waterpipe in the Middle East. The aim of this study was to determine the association between different types of tobacco use and earlier death in the Golestan Cohort Study., Methods: The Study includes 50 045 adults (aged 40-75 years) from north eastern Iran. The baseline questionnaire (2004-2008) assessed information about use of cigarettes, chewing tobacco (nass) and waterpipe. To assess the use of each type of tobacco compared with never tobacco users, we used Cox regression models adjusted for age, socioeconomic status, area of residence, education and other tobacco used, and stratified by sex, ethnicity and opium use., Results: 17% of participants reported a history of cigarette smoking, 7.5% chewing tobacco (nass) and 1.1% smoking waterpipe, and these figures declined in the later birth cohorts. During a median follow-up of 8 years, 4524 deaths occurred (mean age 64.8+9.9 years). Current (HR=1.44; 95% CI 1.28 to 1.61) and former (HR=1.35; 95% CI 1.16 to 1.56) cigarette smokers had higher overall mortality relative to never tobacco users. The highest cigarette-associated risk was for cancer death among current heavy smokers (HR=2.32; 95% CI 1.66 to 3.24). Current nass chewing was associated with overall mortality (HR=1.16; 95% CI 1.01 to 1.34), and there was a 61% higher risk of cancer death in people chewing nass more than five times a day. We observed an association between the cumulative lifetime waterpipe use (waterpipe-years≥28) and both overall (HR=1.66; 95% CI 1.11 to 2.47), and cancer mortality (HR=2.82; 95% CI 1.30 to 6.11)., Conclusions: Regular use of cigarettes, smokeless tobacco and waterpipe were associated with the risk of earlier death (particularly from cancer) in our cohort., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Introduction: Tobacco use remains a leading modifiable cause of cancer incidence and premature mortality in the U.S. and globally. Despite increasing life expectancy worldwide, less is known about the effects of cigarette smoking on older populations. This study sought to determine the effects of smoking on mortality in older age., Methods: Associations of mortality with self-reported age at smoking cessation, age at smoking initiation, and amount smoked after age 70 years were examined in 160,113 participants of the NIH-AARP Diet and Health Study aged >70 years. Participants completed a questionnaire detailing their smoking use in 2004-2005, and were followed for mortality through December 31, 2011. Analyses were conducted between 2014 and 2016., Results: Relative to never smokers, current smokers were more likely to die during follow-up (hazard ratio, 3.18; 95% CI=3.04, 3.31). Furthermore, former smokers had lower risks than current smokers (hazard ratios for quitting between ages 30-39, 40-49, 50-59, and 60-69 years were 0.41 [95% CI=0.39, 0.43], 0.51 [95% CI=0.49, 0.54], 0.64 [95% CI=0.61, 0.67], and 0.77 [95% CI=0.73, 0.81], respectively). Among current smokers, mortality was inversely associated with age at initiation, but directly associated with the number of cigarettes smoked per day at age >70 years., Conclusions: As among younger people, lifetime cigarette smoking history is a key determinant of mortality after age 70 years., (Published by Elsevier Inc.)

Background: Light and/or intermittent smokers have been the fastest growing segment of cigarette smokers in the United States over the past two decades. Defining their behavioral characteristics is a critical public health priority., Methods: Our sample included 78,229 U.S. adults from three pooled contemporary population-based surveys: the 2012 NHIS, 2012 NSDUH, and 2011-2012 NHANES. We classified current smokers into four categories (light and intermittent [LITS], light-daily, heavier-intermittent, and heavier-daily) and assessed smoking behaviors, illicit drug use, and mental health indicators using weighted analyses., Results: Analyses associated smoking categories with nicotine dependence, age of smoking initiation, race/ethnicity, and other demographic and behavioral factors. Compared with heavier-daily smokers, smokers who were LITS were most likely to have mild or no nicotine dependence (weighted odds ratio [OR], 16.92; 95% confidence interval [CI], 13.10-21.85), to start smoking cigarettes regularly after age 21 (OR, 3.42; 95% CI, 2.84-4.12), and to be Hispanic (OR, 5.38; 95% CI, 4.38-6.61). Additional significant results were found for other categories of smokers., Conclusions: Based on pooled data from three large national surveys, light and/or intermittent smokers differed in smoking, drug use, and mental health behaviors from heavier-daily, former, and never smokers. Notable differences by level of smoking frequency and intensity were observed for nicotine dependence, age of smoking initiation, and race/ethnicity., Impact: Our results may help focus preventive measures and policies for the growing number of light and/or intermittent smokers in the United States because smoking patterns vary by behavioral and socioeconomic factors. Cancer Epidemiol Biomarkers Prev; 26(2); 228-39. ©2016 AACR., (©2016 American Association for Cancer Research.)

Importance: A growing proportion of US smokers now smoke fewer than 10 cigarettes per day (CPD), and that proportion will likely rise in the future. The health effects of smoking only a few CPD over one's lifetime are less understood than are the effects of heavier smoking, although many smokers believe that their level is modest., Objective: To evaluate the associations of long-term smoking of fewer than 1 or 1 to 10 CPD (low intensity) with all-cause and cause-specific mortality compared with never smoking cigarettes., Design, Setting, and Participants: Prospective cohort study of 290 215 adults in the National Institutes of Health-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study who were aged 59 to 82 years in calendar years 2004-2005 (baseline). Data were gathered with a questionnaire assessing lifetime cigarette smoking history. Hazard ratios (HRs) and 95% CIs were determined for all-cause mortality and cause-specific mortality through the end of 2011. Hazard ratios and 95% CIs were estimated using Cox proportional hazards regression models using age as the underlying time metric and adjusted for sex, race/ethnicity, educational level, physical activity, and alcohol intake. Data analysis was conducted from December 15, 2015, to September 30, 2016., Exposures: Current and historical smoking intensity during 9 previous age periods (from <15 years to ≥70 years) over the lifetime assessed on the 2004-2005 questionnaire., Main Outcomes and Measures: All-cause and cause-specific mortality among current, former, and never smokers., Results: Of the 290 215 cohort participants who completed the 2004-2005 questionnaire, 168 140 were men (57.9%); the mean (SD) age was 71 (5.3) years (range, 59-82 years). Most people who smoked fewer than 1 or 1 to 10 CPD at baseline reported smoking substantially higher numbers of CPD earlier in their lives. Nevertheless, 159 (9.1%) and 1493 (22.5%) of these individuals reported consistently smoking fewer than 1 or 1 to 10 CPD in each age period that they smoked, respectively. Relative to never smokers, consistent smokers of fewer than 1 CPD (HR, 1.64; 95% CI, 1.07-2.51) and 1 to 10 CPD (HR, 1.87; 95% CI, 1.64-2.13) had a higher all-cause mortality risk. Associations were similar in women and men for all-cause mortality and were observed across a range of smoking-related causes of death, with an especially strong association with lung cancer (HR, 9.12; 95% CI, 2.92-28.47, and HR, 11.61; 95% CI, 8.25-16.35 for <1 and 1-10 CPD, respectively). Former smokers who had consistently smoked fewer than 1 or 1 to 10 CPD had progressively lower risks with younger age at cessation. For example, the HRs for consistent smokers of fewer than 1 and 1 to 10 CPD who quit at 50 years or older were 1.44 (95% CI, 1.12-1.85) and 1.42 (95% CI, 1.27-1.59), respectively., Conclusions and Relevance: This study provides evidence that individuals who smoke fewer than 1 or 1 to 10 CPD over their lifetime have higher mortality risks than never smokers and would benefit from cessation. These results provide further evidence that there is no risk-free level of exposure to tobacco smoke.

In this issue of the Journal, Wyss et al. (Am J Epidemiol. 2016;184(10):703-716) describe the association between use of smokeless tobacco and head and neck cancer in 11 US case-control studies. Despite use by an estimated 300 million people worldwide and prior evidence for a causal association with cancer, these products remain understudied. Data are particularly needed for persons who do not use cigarettes or other smoking tobacco products. With 6,772 cancer cases and 8,375 controls, the current study is larger than previous efforts, allowing evaluation of associations among never cigarette smokers. Importantly, snuff use was positively associated with head and neck cancer, particularly for cancers of the oral cavity, whereas associations were weaker for chewing tobacco. Associations were observed among never cigarette smokers but not among ever cigarette smokers. Yet, despite the large sample size, only 44 cases and 62 controls had used snuff and only 61 cases and 96 controls had used chewing tobacco in the absence of cigarettes, precluding detailed examinations of dose response and cessation. Future studies set in high-prevalence populations with detailed assessment of lifetime use are needed to better understand the cancer risks of exclusive smokeless tobacco use and dual use of smokeless tobacco with other tobacco products, including cigarettes.

Background: The nonessential amino acid cysteine is known to be involved in many antioxidant and anticarcinogenic pathways. Cysteinylglycine is a pro-oxidant metabolite of glutathione and a precursor of cysteine., Objective: To examine the relation between serum cysteine and cysteinylglycine and risk of gastric adenocarcinomas, esophageal squamous cell carcinomas, and head and neck squamous cell carcinomas, we conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study of male Finnish smokers aged 50-69 y at baseline., Design: In total, 170 gastric adenocarcinomas, 68 esophageal squamous cell carcinomas, and 270 head and neck squamous cell carcinomas (identified from the Finnish Cancer Registry) were matched one-to-one with cancer-free control subjects on age and the date of serum collection. We calculated ORs and 95% CIs with the use of a multivariate-adjusted conditional logistic regression., Results: Cysteine had a U-shaped association with gastric adenocarcinomas; a model that included a linear and a squared term had a significant global P-test (P = 0.036). Serum cysteinylglycine was inversely associated with adenocarcinomas of the gastric cardia (OR for above the median compared with below the median: 0.07; 95% CI: 0.01, 0.70; n = 38 cases) but not for other sites. Both cysteine and cysteinylglycine were not associated with esophageal squamous cell carcinoma or head and neck squamous cell carcinoma., Conclusions: We observed associations between serum cysteine and cysteinylglycine with upper gastrointestinal cancer risk. Future studies are needed to replicate these findings. This trial was registered at clininicaltrials.gov as NCT00342992., (© 2016 American Society for Nutrition.)

Background: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality., Methods: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs., Results: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking., Conclusions: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.

Introduction: Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impact and the benefits of smoking cessation among older adults has remained limited. Therefore, we aimed to estimate the influence of smoking and smoking cessation on all-cause mortality in people aged ≥60 years., Methods: Relative mortality and mortality rate advancement periods (RAPs) were estimated by Cox proportional hazards models for the population-based prospective cohort studies from Europe and the U.S. (CHANCES [Consortium on Health and Ageing: Network of Cohorts in Europe and the U.S.]), and subsequently pooled by individual participant meta-analysis. Statistical analyses were performed from June 2013 to March 2014., Results: A total of 489,056 participants aged ≥60 years at baseline from 22 population-based cohort studies were included. Overall, 99,298 deaths were recorded. Current smokers had 2-fold and former smokers had 1.3-fold increased mortality compared with never smokers. These increases in mortality translated to RAPs of 6.4 (95% CI=4.8, 7.9) and 2.4 (95% CI=1.5, 3.4) years, respectively. A clear positive dose-response relationship was observed between number of currently smoked cigarettes and mortality. For former smokers, excess mortality and RAPs decreased with time since cessation, with RAPs of 3.9 (95% CI=3.0, 4.7), 2.7 (95% CI=1.8, 3.6), and 0.7 (95% CI=0.2, 1.1) for those who had quit <10, 10 to 19, and ≥20 years ago, respectively., Conclusions: Smoking remains as a strong risk factor for premature mortality in older individuals and cessation remains beneficial even at advanced ages. Efforts to support smoking abstinence at all ages should be a public health priority., (Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Time to first cigarette (TTFC) after waking is an indicator of nicotine dependence. The association between TTFC and chronic obstructive pulmonary disease (COPD), the third leading cause of death in the United States, has not yet been reported., Methods: We investigated the cross-sectional association between TTFC and prevalent COPD among 6,108 current smokers in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. COPD was defined as a self-reported diagnosis of emphysema, chronic bronchitis, or both. Current smokers in PLCO reported TTFC, the amount of time they typically waited before smoking their first cigarette of the day after waking, in four categories: ≤ 5, 6-30, 31-60, or > 60 minutes. We used logistic regression models to investigate the association between TTFC and prevalent COPD with adjustments for age, gender, race, education, and smoking (cigarettes/day, years smoked during lifetime, pack-years, age at smoking initiation), and prior lung cancer diagnosis., Results: COPD was reported by 19% of these 6,108 smokers. Individuals with the shortest TTFC had the greatest risk of COPD; compared to those with the longest TTFC (> 60 minutes) the adjusted odds ratios (OR) and 95% confidence intervals (CI) for COPD were 1.48 (95% CI, 1.15-1.91), 1.64 (95% CI, 1.29-2.08), 2.18 (95% CI, 1.65-2.87) for those with TTFC 31-60 minutes, 6-30 minutes, and ≤ 5 minutes, respectively (P-trend < 0.0001). The association between TTFC and emphysema was similar to that for bronchitis, albeit the ORs were slightly stronger for chronic bronchitis; comparing TTFC ≤5 minutes to > 60 minutes, the adjusted OR (95% CI) was 2.29 (1.69-3.12) for emphysema and 2.99 (1.95-4.59) for chronic bronchitis., Conclusions: Current smokers with shorter TTFC have increased risk of COPD compared to those with longer TTFC, even after comprehensive adjustment for established smoking covariates. Future epidemiologic studies, including prospective designs, should incorporate TTFC to better assess disease risk and evaluate the potential utility of TTFC as a COPD screening tool for smokers in the clinical setting.

Objective: To investigate the impact of smoking and smoking cessation on cardiovascular mortality, acute coronary events, and stroke events in people aged 60 and older, and to calculate and report risk advancement periods for cardiovascular mortality in addition to traditional epidemiological relative risk measures., Design: Individual participant meta-analysis using data from 25 cohorts participating in the CHANCES consortium. Data were harmonised, analysed separately employing Cox proportional hazard regression models, and combined by meta-analysis., Results: Overall, 503,905 participants aged 60 and older were included in this study, of whom 37,952 died from cardiovascular disease. Random effects meta-analysis of the association of smoking status with cardiovascular mortality yielded a summary hazard ratio of 2.07 (95% CI 1.82 to 2.36) for current smokers and 1.37 (1.25 to 1.49) for former smokers compared with never smokers. Corresponding summary estimates for risk advancement periods were 5.50 years (4.25 to 6.75) for current smokers and 2.16 years (1.38 to 2.39) for former smokers. The excess risk in smokers increased with cigarette consumption in a dose-response manner, and decreased continuously with time since smoking cessation in former smokers. Relative risk estimates for acute coronary events and for stroke events were somewhat lower than for cardiovascular mortality, but patterns were similar., Conclusions: Our study corroborates and expands evidence from previous studies in showing that smoking is a strong independent risk factor of cardiovascular events and mortality even at older age, advancing cardiovascular mortality by more than five years, and demonstrating that smoking cessation in these age groups is still beneficial in reducing the excess risk., (© Mons et al 2015.)

Purpose: Tobacco causes many adverse health conditions and may alter the upper gastrointestinal (UGI) microbiome. However, the few studies that studied the association between tobacco use and the microbiome were small and underpowered. Therefore, we investigated the association between tobacco use and the UGI microbiome in Chinese men., Methods: We included 278 men who underwent esophageal cancer screening in Henan Province, China. Men were categorized as current, former, or never smokers from questionnaire data. UGI tract bacterial cells were characterized using the Human Oral Microbial Identification Microarray. Counts of unique bacterial species and genera estimated alpha diversity. For beta diversity, principal coordinate (PCoA) vectors were generated from an unweighted UniFrac distance matrix. Polytomous logistic regression models were used for most analyses., Results: Of the 278 men in this study, 46.8% were current smokers and 12.6% were former smokers. Current smokers tended to have increased alpha diversity (mean 42.3 species) compared to never smokers (mean 38.9 species). For a 10 species increase, the odds ratio (OR) for current smoking was 1.29 (95% CI 1.04-1.62). Beta diversity was also associated with current smoking. The first two PCoA vectors were strongly associated with current smoking (PCoA1 OR 0.66; 95% CI 0.51-0.87; PCoA2 OR 0.73; 95% CI 0.56-0.95). Furthermore, Dialister invisus and Megasphaera micronuciformis were more commonly detected in current smokers than in never smokers., Conclusions: Current smoking was associated with both alpha and beta diversity in the UGI tract. Future work should consider how the UGI microbiome is associated with smoking-related diseases.

Purpose: The proportion of cancer deaths in the contemporary United States caused by cigarette smoking (the population attributable fraction [PAF]) is not well documented., Methods: The PAF of all cancer deaths due to active cigarette smoking among adults 35 years and older in the United States in 2010 was calculated using age- and sex-specific smoking prevalence from the National Health Interview Survey (NHIS) and age- and sex-specific relative risks from the Cancer Prevention Study-II (for ages 35-54 years) and from the Pooled Contemporary Cohort data set (for ages 55 years and older)., Results: The PAF for active cigarette smoking was 28.7% when estimated conservatively, including only deaths from the 12 cancers currently formally established as caused by smoking by the US Surgeon General. The PAF was 31.7% when estimated more comprehensively, including excess deaths from all cancers. These estimates do not include additional potential cancer deaths from environmental tobacco smoke or other type of tobacco use such as cigars, pipes, or smokeless tobacco., Conclusions: Cigarette smoking causes a large proportion of cancer deaths in the contemporary United States. Reducing smoking prevalence as rapidly as possible should be a top priority for the US public health efforts to prevent cancer deaths., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Data on smoking and second cancer risk among cancer survivors are limited. We assessed associations between smoking before first cancer diagnosis and risk of second primary smoking-associated cancers among survivors of lung (stage I), bladder, kidney, and head/neck cancers., Methods: Data were pooled from 2,552 patients with stage I lung cancer, 6,386 with bladder cancer, 3,179 with kidney cancer, and 2,967 with head/neck cancer from five cohort studies. We assessed the association between prediagnostic smoking and second smoking-associated cancer risk with proportional hazards regression, and compared these estimates to those for first smoking-associated cancers in all cohort participants., Results: Compared with never smoking, current smoking of ≥ 20 cigarettes per day was associated with increased second smoking-associated cancer risk among survivors of stage I lung (hazard ratio [HR] = 3.26; 95% CI, 0.92 to 11.6), bladder (HR = 3.67; 95% CI, 2.25 to 5.99), head/neck (HR = 4.45; 95% CI, 2.56 to 7.73), and kidney cancers (HR = 5.33; 95% CI, 2.55 to 11.1). These estimates were similar to those for first smoking-associated cancer among all cohort participants (HR = 5.41; 95% CI, 5.23 to 5.61). The 5-year cumulative incidence of second smoking-associated cancers ranged from 3% to 8% in this group of cancer survivors., Conclusion: Understanding risk factors for second cancers among cancer survivors is crucial. Our data indicate that cigarette smoking before first cancer diagnosis increases second cancer risk among cancer survivors, and elevated cancer risk in these survivors is likely due to increased smoking prevalence. The high 5-year cumulative risks of smoking-associated cancers among current smoking survivors of stage I lung, bladder, kidney, and head/neck cancers highlight the importance of smoking cessation in patients with cancer., (© 2014 by American Society of Clinical Oncology.)

Background: A comprehensive characterization of the effects of cigarette smoke on systemic soluble immune/inflammatory markers may provide insight into the mechanisms through which smoking causes disease., Methods: Levels of 78 inflammation, immune, and metabolic markers were measured using multiplex immune assays in 1819 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) participants aged 55 to 74 years from three existing nested case-control studies. These data were made representative of the entire PLCO screening arm through reweighting with weights estimated in logistic regression models. We assessed associations between smoking status, cigarettes smoked per day, and time since quitting with dichotomized marker levels using adjusted weighted logistic regression models., Results: Current smoking was associated with 10 inflammation markers after correcting for multiple testing, encompassing several components of the immune/inflammation response. Levels of seven of these markers (interleukin [IL]-15, IL-1RA, IL-1β, IL-16, stem cell factor, soluble interleukin 6 receptor, and soluble vascular endothelial growth factor receptor 3) were lower among current smokers (n = 414) when compared with never smokers (n = 548), with odds ratios (ORs) ranging from 0.44 to 0.27, while levels of CC motif ligand (CCL)/thymus and activation regulated chemokine (CCL17/TARC) (OR = 4.08, 95% confidence interval [CI] = 2.01 to 8.25), CCL11/EOTAXIN (OR = 2.57, 95% CI = 1.45 to 4.55), and C-reactive protein (CRP) (OR = 2.54, 95% CI = 1.29 to 4.98) were elevated. These markers were not associated with cigarettes per day among current smokers, but there were trends in IL-15, IL-1RA, IL-1β, CCL17/TARC, CCL11/EOTAXIN, and CRP levels across categories of years since quitting smoking., Conclusions: Smoking is associated with a broad range of alterations in systemic immune and inflammation marker levels among older, long-term smokers. Smoking cessation may result in marker levels reverting back to those of never smokers over time., (Published by Oxford University Press 2014.)

Colorectal cancer is not strictly considered a tobacco-related malignancy, but modest associations have emerged from large meta-analyses. Most studies, however, use self-reported data, which are subject to misclassification. Biomarkers of tobacco exposure may reduce misclassification and provide insight into metabolic variability that potentially influences carcinogenesis. Our aim was to identify metabolites that represent smoking habits and individual variation in tobacco metabolism, and investigate their association with colorectal cancer. In a nested case-control study of 255 colorectal cancers and 254 matched controls identified in the Prostate, Lung, Colorectal and Ovarian cancer screening trial, baseline serum was used to identify metabolites by ultra-high-performance liquid-phase chromatography and mass spectrometry, as well as gas chromatography with tandem mass spectrometry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Self-reported current smoking was associated with serum cotinine, O-cresol sulfate and hydroxycotinine. Self-reported current smoking of any tobacco (OR = 1.90, 95% CI: 1.02-3.54) and current cigarette smoking (OR = 1.51, 95% CI: 0.75-3.04) were associated with elevated colorectal cancer risks, although the latter was not statistically significant. Individuals with detectable levels of hydroxycotinine had an increased colorectal cancer risk compared with those with undetectable levels (OR = 2.68, 95% CI: 1.33-5.40). Although those with detectable levels of cotinine had a suggestive elevated risk of this malignancy (OR = 1.81, 95% CI: 0.98-3.33), those with detectable levels of O-cresol sulfate did not (OR = 1.16, 95% CI: 0.57-2.37). Biomarkers capturing smoking behavior and metabolic variation exhibit stronger associations with colorectal cancer than self-report, providing additional evidence for a role for tobacco in this malignancy., (Published by Oxford University Press 2014.)

Background: Targeting smokers at higher lung cancer risk can improve efficiency and reduce false-positive detection in lung cancer screening. We evaluated whether time to first cigarette after waking (TTFC), a single-item measure of nicotine dependency, could improve stratification of lung cancer risk beyond standard smoking metrics (intensity, duration, and pack-years)., Methods: In 3249 ever-smokers (n = 1812 case subjects; n = 1437 control subjects) from a population-based case-control study in Italy, we examined the association between TTFC and lung cancer using logistic regression and estimated lung cancer incidence by levels of TTFC, and intensity, duration, and pack-years using absolute risk regression. Significance tests were two-sided., Results: Compared with smokers with TTFC greater than 60 minutes, the lung cancer odds ratios for TTFC of 31 to 60 minutes, 6 to 30 minutes, and 5 or fewer minutes (by increasing dependency) were 2.57 (95% confidence interval [CI] = 2.03 to 3.26), 2.27 (95% CI = 1.79 to 2.88), and 3.50 (95% CI = 2.64 to 4.64), respectively (P trend < .0001). The average lung cancer incidence rates for smokers of 1 to 10, 11 to 20, 21 to 30 and more than 30 cigarettes per day were consistently higher among smokers with TTFC of 60 or fewer minutes vs more than 60 minutes (64.1 vs 11.7; 125.6 vs 28.6; 130.1 vs 40.7; and 260.8 vs 108.9 per 100000 person-years, respectively). The slopes of increase in lung cancer rates with smoking duration and pack-years were statistically significantly greater among smokers with higher dependency (P interaction < .001)., Conclusions: Lung cancer risk increases with shorter TTFC; this simple nicotine dependency measure increases lung cancer risk stratification beyond standard smoking measures. Assessing TTFC may improve lung cancer risk prediction and could be useful in lung cancer screening and smoking cessation programs., (Published by Oxford University Press 2014.)

Objective: Water-pipe and smokeless tobacco use have been associated with several adverse health outcomes. However, little information is available on the association between water-pipe use and heart disease (HD). Therefore, we investigated the association of smoking water-pipe and chewing nass (a mixture of tobacco, lime and ash) with prevalent HD., Design: Cross-sectional study., Setting: Baseline data (collected in 2004-2008) from a prospective population-based study in Golestan Province, Iran., Participants: 50 045 residents of Golestan (40-75 years old; 42.4% men)., Main Outcome Measures: ORs and 95% CIs from multivariate logistic regression models for the association of water-pipe and nass use with HD prevalence., Results: A total of 3051 (6.1%) participants reported a history of HD, and 525 (1.1%) and 3726 (7.5%) reported ever water-pipe or nass use, respectively. Heavy water-pipe smoking was significantly associated with HD prevalence (highest level of cumulative use vs never use, OR=3.75; 95% CI 1.52 to 9.22; p for trend=0.04). This association persisted when using different cut-off points, when restricting HD to those taking nitrate compound medications, and among never cigarette smokers. There was no significant association between nass use and HD prevalence (highest category of use vs never use, OR=0.91; 95% CI 0.69 to 1.20)., Conclusions: Our study suggests a significant association between HD and heavy water-pipe smoking. Although the existing evidence suggesting similar biological consequences of water-pipe and cigarette smoking make this association plausible, results of our study were based on a modest number of water-pipe users and need to be replicated in further studies.

Background: The disease risks from cigarette smoking increased in the United States over most of the 20th century, first among male smokers and later among female smokers. Whether these risks have continued to increase during the past 20 years is unclear., Methods: We measured temporal trends in mortality across three time periods (1959-1965, 1982-1988, and 2000-2010), comparing absolute and relative risks according to sex and self-reported smoking status in two historical cohort studies and in five pooled contemporary cohort studies, among participants who became 55 years of age or older during follow-up., Results: For women who were current smokers, as compared with women who had never smoked, the relative risks of death from lung cancer were 2.73, 12.65, and 25.66 in the 1960s, 1980s, and contemporary cohorts, respectively; corresponding relative risks for male current smokers, as compared with men who had never smoked, were 12.22, 23.81, and 24.97. In the contemporary cohorts, male and female current smokers also had similar relative risks for death from chronic obstructive pulmonary disease (COPD) (25.61 for men and 22.35 for women), ischemic heart disease (2.50 for men and 2.86 for women), any type of stroke (1.92 for men and 2.10 for women), and all causes combined (2.80 for men and 2.76 for women). Mortality from COPD among male smokers continued to increase in the contemporary cohorts in nearly all the age groups represented in the study and within each stratum of duration and intensity of smoking. Among men 55 to 74 years of age and women 60 to 74 years of age, all-cause mortality was at least three times as high among current smokers as among those who had never smoked. Smoking cessation at any age dramatically reduced death rates., Conclusions: The risk of death from cigarette smoking continues to increase among women and the increased risks are now nearly identical for men and women, as compared with persons who have never smoked. Among men, the risks associated with smoking have plateaued at the high levels seen in the 1980s, except for a continuing, unexplained increase in mortality from COPD.

The authors prospectively examined whether caffeine intake was associated with lower risk of Parkinson disease (PD) in both men and women among 304,980 participants in the National Institutes of Health-AARP Diet and Health Study and whether smoking affected this relation. Multivariate odds ratios and 95% confidence intervals were derived from logistic regression models. Higher caffeine intake as assessed in 1995-1996 was monotonically associated with lower PD risk (diagnosed in 2000-2006) in both men and women. After adjustment for age, race, and physical activity, the odds ratio comparing the highest quintile of caffeine intake with the lowest was 0.75 (95% confidence interval: 0.60, 0.94; P(trend) = 0.005) for men and 0.60 (95% confidence interval: 0.39, 0.91; P(trend) = 0.005) for women. Further adjustment for duration of smoking and analyses carried out among never smokers showed similar results. A joint analysis with smoking suggested that smoking and caffeine may act independently in relation to PD risk. Finally, the authors conducted a meta-analysis of prospective studies and confirmed that caffeine intake was inversely associated with PD risk in both men and women. These findings suggest no gender difference in the relation between caffeine and PD.

Background: Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration., Methods: The authors pooled data from 12 case-control studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1242 (EAC), 1263 (EGJA) and 954 (ESCC) cases and 7053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux., Results: For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P<0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5 drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P=0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P<0.01)., Conclusions: Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases., (Published by Elsevier Ltd.)

Background: Although obesity has been directly linked to the development of many cancers, many epidemiological studies have found that body mass index (BMI)--a surrogate marker of obesity--is inversely associated with the risk of lung cancer. These studies are difficult to interpret because of potential confounding by cigarette smoking, a major risk factor for lung cancer that is associated with lower BMI., Methods: We prospectively examined the association between BMI and the risk of lung cancer among 448 732 men and women aged 50-71 years who were recruited during 1995-1996 for the National Institutes of Health-AARP Diet and Health Study. BMI was calculated based on the participant's self-reported height and weight on the baseline questionnaire. We identified 9437 incident lung carcinomas (including 415 in never smokers) during a mean follow-up of 9.7 years through 2006. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for lung cancer risk factors, including smoking status. To address potential bias due to preexisting undiagnosed disease, we excluded potentially unhealthy participants in sensitivity analyses. All statistical tests were two-sided., Results: The crude incidence rate of lung cancer over the study follow-up period was 233 per 100 000 person-years among men and 192 per 100 000 person-years among women. BMI was inversely associated with the risk of lung cancer among both men and women (BMI ≥35 vs 22.5-24.99 kg/m(2): HR = 0.81, 95% CI = 0.70 to 0.94 and HR = 0.73, 95% CI = 0.61 to 0.87, respectively). The inverse association was restricted to current and former smokers and was stronger after adjustment for smoking. Among smokers, the inverse association persisted even after finely stratifying on smoking status, time since quitting smoking, and number of cigarettes smoked per day. Sensitivity analyses did not support the possibility that the inverse association was due to prevalent undiagnosed disease., Conclusions: Our results suggest that a higher BMI is associated with a reduced risk of lung cancer in current and former smokers. Our inability to attribute the inverse association between BMI and the risk of lung cancer to residual confounding by smoking or to bias suggests the need for considering other explanations.

Context: Previous studies indicate that the population attributable risk (PAR) of bladder cancer for tobacco smoking is 50% to 65% in men and 20% to 30% in women and that current cigarette smoking triples bladder cancer risk relative to never smoking. During the last 30 years, incidence rates have remained stable in the United States in men (123.8 per 100,000 person-years to 142.2 per 100,000 person-years) and women (32.5 per 100,000 person-years to 33.2 per 100,000 person-years); however, changing smoking prevalence and cigarette composition warrant revisiting risk estimates for smoking and bladder cancer., Objective: To evaluate the association between tobacco smoking and bladder cancer., Design, Setting, and Participants: Men (n = 281,394) and women (n = 186,134) of the National Institutes of Health-AARP (NIH-AARP) Diet and Health Study cohort completed a lifestyle questionnaire and were followed up between October 25, 1995, and December 31, 2006. Previous prospective cohort studies of smoking and incident bladder cancer were identified by systematic review and relative risks were estimated from fixed-effects models with heterogeneity assessed by the I(2) statistic., Main Outcome Measures: Hazard ratios (HRs), PARs, and number needed to harm (NNH)., Results: During 4,518,941 person-years of follow-up, incident bladder cancer occurred in 3896 men (144.0 per 100,000 person-years) and 627 women (34.5 per 100,000 person-years). Former smokers (119.8 per 100,000 person-years; HR, 2.22; 95% confidence interval [CI], 2.03-2.44; NNH, 1250) and current smokers (177.3 per 100,000 person-years; HR, 4.06; 95% CI, 3.66-4.50; NNH, 727) had higher risks of bladder cancer than never smokers (39.8 per 100,000 person-years). In contrast, the summary risk estimate for current smoking in 7 previous studies (initiated between 1963 and 1987) was 2.94 (95% CI, 2.45-3.54; I(2) = 0.0%). The PAR for ever smoking in our study was 0.50 (95% CI, 0.45-0.54) in men and 0.52 (95% CI, 0.45-0.59) in women., Conclusion: Compared with a pooled estimate of US data from cohorts initiated between 1963 and 1987, relative risks for smoking in the more recent NIH-AARP Diet and Health Study cohort were higher, with PARs for women comparable with those for men.

Background: Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose-response, and duration of cigarette smoking cessation., Methods: We used primary data from 10 population-based case-control studies and two cohort studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided., Results: The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose-response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (<10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and > or =10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar., Conclusions: Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks.

Increased physical activity has been associated with decreased lung cancer risk. However, no previous investigation has examined physical activity in relation to lung cancer histologic types by smoking status. The authors investigated these relations in the National Institutes of Health-AARP Diet and Health Study among 501,148 men and women aged 50-71 years at baseline in 1995-1996. During follow-up to 2003, 6,745 lung carcinomas occurred (14.8% small cell, 40.3% adenocarcinoma, 19.7% squamous cell, 6.1% undifferentiated large cell, 7.2% non-small cell not otherwise specified, and 11.8% carcinoma not otherwise specified). Among former smokers, the multivariate relative risks of small cell, adenocarcinoma, squamous cell, and undifferentiated large cell carcinomas comparing the highest with the lowest activity level (> or =5 times/week vs. inactive) were 0.93 (95% confidence interval (CI): 0.67, 1.28), 0.79 (95% CI: 0.67, 0.94), 0.73 (95% CI: 0.57, 0.93), and 0.61 (95% CI: 0.38, 0.98), respectively. Among current smokers, corresponding values were 0.77 (95% CI: 0.58, 1.02), 0.76 (95% CI: 0.61, 0.95), 0.85 (95% CI: 0.65, 1.11), and 1.10 (95% CI: 0.69, 1.78). In contrast, physical activity was unrelated to lung carcinoma among never smokers (P(interaction) between physical activity and smoking for total lung carcinomas = 0.002). The inverse findings among former and current smokers in combination with the null results for physical activity among never smokers may point toward residual confounding by cigarette smoking as an explanation for the relations observed.

Background: Whether women are more susceptible than men to lung cancer caused by cigarette smoking has been controversial. To address this question, we aimed to compare incidence rates of lung cancer by stratum of smoking use in men and women of the National Institutes of Health (NIH)-AARP cohort., Methods: Participants in the NIH-AARP Diet and Health study responded to a postal questionnaire between Oct 13, 1995, and May 6, 1996, and were followed up until Dec 31, 2003. The questionnaire asked participants about their past and current smoking status, demographics, alcohol intake, tobacco smoking, physical activity, and included a food-frequency questionnaire of 124 items. Incident lung cancers were identified by linkage to individual state cancer registries. We present age-standardised incidence rates for cancer and multivariate hazard ratios (HRs) adjusted for potential confounders, with 95% CIs. This study conforms to the STROBE guidelines., Findings: 279 214 men and 184 623 women from eight states in the USA aged 50-71 years at study baseline were included in this analysis. During follow-up, lung cancers occurred in 4097 men and 2237 women. Incidence rates were 20.3 (95% CI 16.3-24.3) per 100 000 person-years in men who had never smoked (99 cancers) and 25.3 (21.3-29.3) in women who had never smoked (152 cancers); for this group, the adjusted HR for lung cancer was 1.3 (1.0-1.8) for women compared with men. Smoking was associated with increased risk of lung cancer in men and women. The incidence rate of current smokers who smoked more than two packs per day was 1259.2 (1035.0-1483.3) in men and 1308.9 (924.2-1693.6) in women. In current smokers, in a model adjusted for typical smoking dose, the HR was 0.9 (0.8-0.9) for women compared with men. For former smokers, in a model adjusted for years of cessation and typical smoking dose, the HR was 0.9 (0.9-1.0) for women compared with men. Incidence rates of adenocarcinoma, small-cell carcinoma, and undifferentiated tumours were similar in men and women; incidence rates of squamous tumours in men were about twice that in women., Interpretation: Our findings suggest that women are not more susceptible than men to the carcinogenic effects of cigarette smoking in the lung. In smokers, incidence rates tended to be higher in men than women with comparable smoking histories, but differences were modest; smoking was strongly associated with lung cancer risk in both men and women. Future studies should confirm whether incidence rates are indeed higher in women who have never smoked than in men who have never smoked.

Background: Men are approximately 3 times more likely to develop squamous cancers of the head and neck (oral cavity, pharynx, and larynx) than women. Very few prospective studies have examined the association between cigarette smoking and cancers of the head and neck in women, even though the rates of smoking in women are increasing rapidly worldwide., Methods: The association between cigarette smoking and head and neck cancer was investigated in 476,211 participants, aged 50-71 years, of the National Institutes of Health/American Association of Retired Persons (NIH-AARP) diet and health study by using age-standardized incidence rates and hazard ratios from Cox models adjusted for other risk factors for these cancers., Results: Over the course of follow-up (1995 through 2000), 584 men and 175 women were diagnosed with head and neck cancer. Nonsmoking (24.4), former smoking (36.9), and current smoking (147.3) men had higher rates of incident head and neck cancer per 100,000 person-years of follow-up than women did in each equivalent category of cigarette use (non: 4.8; former: 17.2; current: 75.7). The hazard ratios associated with smoking were significantly larger in women (12.96; 95% confidence interval [CI], 7.81-21.52) than in men (5.45, 95% CI, 4.22-7.05; P for interaction: <.001) for head and neck cancer overall and also for the 3 subsites (oral cavity, oro-hypopharynx, and larynx) examined in stratified analyses. Ever-smoking accounted for 45% of head and neck cancers in men and 75% in women, assuming causality., Conclusions: Cigarette smoking is a strong risk factor for head and neck cancer in both men and women. Incidence rates of head and neck cancer were higher in male smokers than female smokers, but smoking may explain a higher proportion of head and neck cancer in women than in men.

Rates of esophageal adenocarcinoma and gastric cardia adenocarcinoma have increased, while rates of esophageal squamous cell carcinoma (ESCC) and gastric noncardia adenocarcinoma have decreased, suggesting distinct etiologies. The authors prospectively investigated the associations of alcohol and tobacco with these cancers in 474,606 US participants using Cox models adjusted for potential confounders. Between 1995/1996 and 2000, 97 incident cases of ESCC, 205 of esophageal adenocarcinoma, 188 of gastric cardia, and 187 of gastric noncardia cancer occurred. Compared with nonsmokers, current smokers were at increased risk for ESCC (hazard ratio (HR) = 9.27, 95% confidence interval (CI): 4.04, 21.29), esophageal adenocarcinoma (HR = 3.70, 95% CI: 2.20, 6.22), gastric cardia (HR = 2.86, 95% CI: 1.73, 4.70), and gastric noncardia (HR = 2.04, 95% CI: 1.32, 3.16). Assuming causality, ever smoking had population attributable risks of 77% (95% CI: 0.55, 0.89) for ESCC, 58% (95% CI: 0.38, 0.72) for esophageal adenocarcinoma, 47% (95% CI: 0.27, 0.63) for gastric cardia, and 19% (95% CI: 0.00, 0.37) for gastric noncardia. For drinkers of more than three alcoholic beverages per day, compared with those whose intake was up to one drink per day, the authors found significant associations between alcohol intake and ESCC risk (HR = 4.93, 95% CI: 2.69, 9.03) but not risk for esophageal, gastric cardia, or gastric noncardia adenocarcinoma.

Background Reducing cigarettes per day may lower the risk of lung cancer compared with continuing to smoke at the same intensity. Other changes in smoking behaviors, such as increasing cigarette consumption or quitting for a period and relapsing, may also affect lung cancer risk. Methods We examined changes in smoking status and cigarettes per day among 24 613 Finnish male smokers aged 50-69 years who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Longitudinal data on smoking were collected during study follow-up visits 3 times a year (approximately every 4 months) between 1985 and 1993. Incident lung cancer patients through 2012 were identified by the Finnish Cancer Registry. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Results Compared with smoking 20 cigarettes per day continuously across the intervention period, reducing an average of 5 cigarettes per day per year while smoking was associated with a 20% lower risk of lung cancer (95% CI = 0.71 to 0.90). A substantially lower risk of lung cancer was also observed when participants smoked at 50% (RR = 0.72, 95% CI = 0.57 to 0.90) and 10% (RR = 0.55, 95% CI = 0.36 to 0.83) of study visits, relative to smoked at 100% of study visits. Conclusions Smokers may lower their risk of lung cancer by reducing smoking intensity (cigarettes per day while smoking) and the time they smoke. However, quitting smoking completely is the most effective way for smokers to reduce their risk of lung cancer. [ABSTRACT FROM AUTHOR]

Background In the United States, lung cancer death rates have been declining for decades, primarily as a result of pronounced decreases in cigarette smoking. It is unclear, however, whether there have been similar declines in mortality rates of lung cancer unrelated to smoking. We estimated trends in US lung cancer death rates attributable and not attributable to smoking from 1991 to 2018. Methods The study included 30- to 79-year-olds in the National Health Interview Survey who were linked to the National Death Index, 1991-2014. Adjusted hazard ratios for smoking status and lung cancer death were estimated, and age-specific population attributable fractions were calculated. Annual population attributable fractions were multiplied by annual US national lung cancer mortality, partitioning rates into smoking-attributable and smoking-unrelated lung cancer deaths. All statistical tests were 2-sided. Results During 1991-2018, the proportion of never smokers increased among both men (35.1%-54.6%) and women (54.0%-65.4%). Compared with those who had ever smoked, those who had never smoked had 86% lower risk (hazard ratio = 0.14; 95% confidence interval [CI] = 0.12 to 0.16) of lung cancer death. The fraction of lung cancer deaths attributable to smoking decreased from 81.4% (95% CI = 78.9 to 81.4) to 74.7% (95% CI = 78.1 to 71.4). Smoking-attributable lung cancer death rates declined 2.7% per year (95% CI = ‒2.9% to ‒2.5%) and smoking-unrelated lung cancer death rates declined 1.8% per year (95% CI = ‒2.0% to ‒1.5%); these declines have accelerated in recent years. Conclusions An increasing proportion of lung cancer deaths are unrelated to smoking based on declines in smoking prevalence. Smoking-unrelated lung cancer death rates have declined, however, perhaps because of decreases in secondhand smoke and air pollution exposure as well as treatment improvements. [ABSTRACT FROM AUTHOR]

Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS). Methods. We analyzed MUCA concentration in 177 GCS participants' urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model. Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (∼6 h) of MUCA. Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggested associations between the oral microbiome and lung cancer, but studies were predominantly cross-sectional and underpowered.Methods: Using a case-cohort design, 1306 incident lung cancer cases were identified in the Agricultural Health Study; National Institutes of Health-AARP Diet and Health Study; and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Referent subcohorts were randomly selected by strata of age, sex, and smoking history. DNA was extracted from oral wash specimens using the DSP DNA Virus Pathogen kit, the 16S rRNA gene V4 region was amplified and sequenced, and bioinformatics were conducted using QIIME 2. Hazard ratios and 95% confidence intervals were calculated using weighted Cox proportional hazards models.Results: Higher alpha diversity was associated with lower lung cancer risk (Shannon index hazard ratio = 0.90, 95% confidence interval = 0.84 to 0.96). Specific principal component vectors of the microbial communities were also statistically significantly associated with lung cancer risk. After multiple testing adjustment, greater relative abundance of 3 genera and presence of 1 genus were associated with greater lung cancer risk, whereas presence of 3 genera were associated with lower risk. For example, every SD increase in Streptococcus abundance was associated with 1.14 times the risk of lung cancer (95% confidence interval = 1.06 to 1.22). Associations were strongest among squamous cell carcinoma cases and former smokers.Conclusions: Multiple oral microbial measures were prospectively associated with lung cancer risk in 3 US cohort studies, with associations varying by smoking history and histologic subtype. The oral microbiome may offer new opportunities for lung cancer prevention. [ABSTRACT FROM AUTHOR]

Background: Increasing proportions of smokers in Japan smoke <10 cigarettes per day (CPD). Yet, the health risks of low-intensity smoking in Asia are poorly understood.Methods: We performed a pooled analysis of 410 294 adults from nine population-based prospective cohort studies participating in the Japan Cohort Consortium. Cigarette-use data were collected at each study baseline in 1983-1994. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality were calculated using multivariable-adjusted Cox regression by CPD among current smokers and by age at cessation among former smokers, with never smokers as the referent group. Pooled HRs and CIs were computed using a random-effect model.Results: The smoking prevalence was 54.5% in men and 7.4% in women. About 15.5% of male and 50.4% of female current smokers smoked 1-10 CPD (low-intensity). Both male and female low-intensity smokers had higher all-cause mortality risks than never smokers. Risks were further higher with increasing CPD in a dose-response manner. HRs (95% CIs) were 1.27 (0.97-1.66), 1.45 (1.33-1.59) and 1.49 (1.38-1.62) for 1-2, 3-5 and 6-10 CPD, respectively, in men; 1.28 (1.01-1.62), 1.49 (1.34-1.66) and 1.68 (1.55-1.81) for 1-2, 3-5 and 6-10 CPD, respectively, in women. Similar associations were observed for smoking-related causes of death. Among former low-intensity smokers, younger age at cessation was associated with lower mortality risk.Conclusions: Smoking very low amounts was associated with increased mortality risks in Japan. All smokers should quit, even if they smoke very few CPD. [ABSTRACT FROM AUTHOR]

Increasing numbers of adults in the United States use more than 1 tobacco product. Most use cigarettes in combination with other tobacco products. However, little is known about the all-cause and cancer-specific mortality risks of dual– and poly–tobacco-product use. We examined these associations by pooling nationally representative data from the 1991, 1992, 1998, 2000, 2005, and 2010 National Health Interview Surveys (n = 118,144). Mortality information was obtained through linkage to the National Death Index. Cigarette smokers who additionally used other tobacco products smoked as many if not more cigarettes per day than exclusive cigarette smokers. Furthermore, cigarette smokers who additionally used other tobacco products had mortality risks that were as high as and sometimes higher than those of exclusive cigarette smokers. As tobacco use patterns continue to change and diversify, investigators in future studies need to carefully assess the impact of noncigarette tobacco products on cigarette use and determine associated disease risks. [ABSTRACT FROM AUTHOR]