Tobacco Use and Respiratory Symptoms Among Adults: Findings From the Longitudinal Population Assessment of Tobacco and Health (PATH) Study 2014-2016.

INTRODUCTION: We examined the relationship between current tobacco use and functionally important respiratory symptoms. METHODS: Longitudinal cohort study of 16 295 US adults without COPD in Waves 2-3 (W2-3, 2014-2016) of the Population Assessment of Tobacco and Health Study. Exposure-Ten mutually exclusive categories of tobacco use including single product, multiple product, former, and never use (reference). Outcome-Seven questions assessing wheezing/cough were summed to create a respiratory symptom index; cutoffs of ≥2 and ≥3 were associated with functional limitations and poorer health. Multivariable regressions examined both cutoffs cross-sectionally and change over approximately 12 months, adjusting for confounders. RESULTS: All tobacco use categories featuring cigarettes (>2/3's of users) were associated with higher risk (vs. never users) for functionally important respiratory symptoms at W2, for example, at symptom severity ≥ 3, risk ratio for exclusive cigarette use was 2.34 [95% CI, 1.92, 2.85] and for worsening symptoms at W3 was 2.80 [2.08, 3.76]. There was largely no increased symptom risk for exclusive use of cigars, smokeless tobacco, hookah, or e-cigarettes (adjustment for pack-years and marijuana attenuated the cross-sectional e-cigarette association from 1.53(95% CI 0.98, 2.40) to 1.05 (0.67, 1.63); RRs for these products were also significantly lower compared to exclusive use of cigarettes. The longitudinal e-cigarette-respiratory symptom association was sensitive to the respiratory index cutoff level; exclusive e-cigarette use was associated with worsening symptoms at an index cutoff ≥ 2 (RR = 1.63 [1.02, 2.59]) and with symptom improvement at an index cutoff of ≥ 3 (RR = 1.64 [1.04, 2.58]). CONCLUSIONS: Past and current cigarette smoking drove functionally important respiratory symptoms, while exclusive use of other tobacco products was largely not associated. However, the relationship between e-cigarette use and symptoms was sensitive to adjustment for pack-years and symptom severity. IMPLICATIONS: How noncigarette tobacco products affect respiratory symptoms is not clear; some studies implicate e-cigarettes. We examined functionally important respiratory symptoms (wheezing/nighttime cough) among US adults without COPD. The majority of adult tobacco users smoke cigarettes and have higher risk of respiratory symptoms and worsening of symptoms, regardless of other products used with them. Exclusive use of other tobacco products (e-cigarettes, cigars, smokeless, hookah) was largely not associated with functionally important respiratory symptoms and risks associated with their use was significantly lower than for cigarettes. The association for e-cigarettes was greatly attenuated by adjustment for cigarette pack-years and sensitive to how symptoms were defined.

Cigarette Smoking Reduction and Health Risks: A Systematic Review and Meta-analysis.

INTRODUCTION: Studies have shown the health benefits of cigarette smoking cessation. However, the literature remains unclear about the relationship between smoking reduction and health risks. This comprehensive review and meta-analysis updates previous reviews with the newest estimates. AIMS AND METHODS: We conducted a systematic review and meta-analysis evaluating the association between smoking reduction and some health risks in observational studies. We defined the following smoking categories: heavy smokers smoked ≥15-20 cigarettes per day (CPD), moderate smokers smoked 10-19 CPD, and light smokers smoked <10 CPD. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random-effect models. RESULTS: We identified 19 studies including four case-control and 15 cohort studies. Compared with continuing heavy smokers, we found decreased lung cancer risk for those who reduced CPD by more than 50% (RR = 0.72, 95% CI: 0.52, 0.91), from heavy to moderate (RR = 0.66, 95% CI: 0.46, 0.85), and from heavy to light (RR = 0.60, 95% CI: 0.49, 0.72). We also found lower risk of cardiovascular disease (CVD) for those who reduced from heavy to light smoking (RR = 0.78, 95% CI: 0.67, 0.89) but not those who reduced by more than 50% and reduced smoking from heavy to moderate. We did not find any significant difference in all-cause mortality, all-cancer risks, and smoking-/tobacco-related cancer risk among those who reduced. CONCLUSIONS: Substantial smoking reduction may decrease lung cancer risk but results on CVD (coronary heart disease and stroke combined) risk were mixed. The relationships between smoking reduction and other endpoints examined were not significant. IMPLICATIONS: This meta-analysis helps clarify our understanding of various smoking reduction levels on some health risks. While smoking reduction may decrease risks of lung cancer, the relationships between smoking reduction and other endpoints, including all-cause mortality and cardiovascular disease, remain unclear. Although smoking reduction may decrease lung cancer risks, the magnitude of lung cancer risk remain high. Among smokers, complete cessation remains the most effective approach for cancer and CVD prevention.

Patterns of tobacco use and nicotine dependence among youth, United States, 2017-2018.

This study examined patterns of tobacco product use and their association with nicotine dependence among U.S. youth. Combined data from the 2017-2018 National Youth Tobacco Surveys were analyzed for students that reported current (past-30-day) use of e-cigarettes, cigarettes, cigars, smokeless tobacco, or hookah (n = 6106). Analyses assessed multiple product use (≥2 tobacco products) overall and by sex, school level, race/ethnicity, current use, and frequent use (use of a product for ≥20 of the preceding 30 days). Multivariable logistic regression was used to identify correlates of nicotine dependence. During 2017-2018, 40.8% of tobacco product users reported use of multiple products. Multiple product use ranged from 47.0% among e-cigarette users to 80.7% among cigarette smokers. Among frequent users of each respective product, 80.0% of cigarette smokers, 74.9% of cigar smokers, 73.6% of smokeless tobacco users, 70.7% of hookah smokers, and 40.3% of e-cigarette users reported use of multiple products. Most youth who reported nicotine dependence (64.0%) were multiple product users. E-cigarettes were the most common single product used (36.3%) and the product most commonly used in combination with other products; e-cigarettes plus cigarettes (6.7%) was the most common product combination. Combustible product use, smokeless tobacco use, multiple product use and frequent use were associated with greater odds of nicotine dependence. Nicotine dependence among youth is especially influenced by cigarette use, smokeless tobacco use, frequent use of any tobacco product, and multiple product use. Proven tobacco control interventions in coordination with regulatory efforts can reduce youth tobacco product use.

Longitudinal pathways of exclusive and polytobacco cigarette use among youth, young adults and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: Cigarettes are the most harmful and most prevalent tobacco product in the USA. This study examines cross-sectional prevalence and longitudinal pathways of cigarette use among US youth (12-17 years), young adults (18-24 years) and adults 25+ (25 years and older). DESIGN: Data were drawn from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US adults and youth. Respondents with data at all three waves (youth, N=11 046; young adults, N=6478; adults 25+, N=17 188) were included in longitudinal analyses. RESULTS: Among Wave 1 (W1) any past 30-day (P30D) cigarette users, more than 60%, persistently used cigarettes across three waves in all age groups. Exclusive cigarette use was more common among adult 25+ W1 P30D cigarette users (62.6%), while cigarette polytobacco use was more common among youth (57.1%) and young adults (65.2%). Persistent exclusive cigarette use was the most common pathway among adults 25+ and young adults; transitioning from exclusive cigarette use to cigarette polytobacco use was most common among youth W1 exclusive cigarette users. For W1 youth and young adult cigarette polytobacco users, the most common pattern of use was persistent cigarette polytobacco use. CONCLUSIONS: Cigarette use remains persistent across time, regardless of age, with most W1 P30D smokers continuing to smoke at all three waves. Policy efforts need to continue focusing on cigarettes, in addition to products such as electronic nicotine delivery systems that are becoming more prevalent.

Longitudinal transitions of exclusive and polytobacco electronic nicotine delivery systems (ENDS) use among youth, young adults and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: Electronic nicotine delivery systems (ENDS; including e-cigarettes) are rapidly evolving in the US marketplace. This study reports cross-sectional prevalence and longitudinal pathways of ENDS use across 3 years, among US youth (12-17 years), young adults (18-24 years) and adults 25+ (25 years and older). DESIGN: Data were from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth and adults. Respondents with data at all three waves (youth, n=11 046; young adults, n=6478; adults 25+, n=17 188) were included in longitudinal analyses. RESULTS: Weighted cross-sectional ever use of ENDS increased at each wave. Across all three waves, young adults had the highest percentages of past 12-month, past 30-day (P30D) and daily P30D ENDS use compared with youth and adults 25+. Only about a quarter of users had persistent P30D ENDS use at each wave. Most ENDS users were polytobacco users. Exclusive Wave 1 ENDS users had a higher proportion of subsequent discontinued any tobacco use compared with polytobacco ENDS users who also used cigarettes. CONCLUSIONS: ENDS use is most common among young adults compared with youth and adults 25+. However, continued use of ENDS over 2 years is not common for any age group. Health education efforts to reduce the appeal and availability of ENDS products might focus on reducing ENDS experimentation, and on reaching the smaller subgroups of daily ENDS users to better understand their reasons for use.

Longitudinal pathways of exclusive and polytobacco hookah use among youth, young adults and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: The goal of this study is to examine cross-sectional rates of use and longitudinal pathways of hookah use among US youth (ages 12-17), young adults (ages 18-24), and adults 25+ (ages 25 and older). DESIGN: Data were drawn from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US adults and youth. Respondents with data at all three waves (youth, n=11 046; young adults, n=6478; adults 25+, n=17 188) were included in longitudinal analyses. RESULTS: Young adults had higher ever, past 12-month (P12M) and past 30-day cross-sectional prevalence of hookah use at each wave than youth or adults 25+. The majority of Wave 1 (W1) hookah users were P12M users of other tobacco products (youth: 73.9%, young adults: 80.5%, adults 25+: 83.2%). Most youth and adult W1 P12M hookah users discontinued use in Wave 2 or Wave 3 (youth: 58.0%, young adults: 47.5%, adults 25+: 63.4%). Most W1 P12M hookah polytobacco users used cigarettes (youth: 49.4%, young adults: 59.4%, adults 25+: 63.2%) and had lower rates of quitting all tobacco than exclusive hookah users or hookah polytobacco users who did not use cigarettes. CONCLUSIONS: Hookah use is more common among young adults than among youth or adults 25+. Discontinuing hookah use is the most common pathway among exclusive or polytobacco hookah users. Understanding longitudinal transitions in hookah use is important in understanding behavioural outcomes at the population level.

Longitudinal pathways of exclusive and polytobacco cigar use among youth, young adults and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: The goal of this study is to examine the cross-sectional prevalence of use and 3-year longitudinal pathways of cigar use in US youth (12-17 years), young adults (18-24 years), and adults 25+ (25 years or older). DESIGN: Data were drawn from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth and adults. Respondents with data at all three waves (youth, n=11 046; young adults, n=6478; adults 25+, n=17 188) were included in longitudinal analyses. RESULTS: Weighted cross-sectional prevalence of past 30-day (P30D) use was stable for adults 25+ (~6%), but decreased in youth (Wave 1 (W1) to Wave 3 (W3)=2.5% to 1.2%) and young adults (W1 to W3=15.7% to 14.0%). Among W1 P30D cigar users, over 50% discontinued cigar use (irrespective of other tobacco use) by Wave 2 (W2) or W3. Across age groups, over 70% of W1 P30D cigar users also indicated P30D use of another tobacco product, predominantly cigar polytobacco use with cigarettes. Discontinuing all tobacco use by W2 or W3 was greater in adult exclusive P30D cigar users compared with polytobacco cigar users. CONCLUSIONS: Although the majority of P30D cigar users discontinued use by W3, adult polytobacco users of cigars were less likely to discontinue all tobacco use than were exclusive cigar users. Tracking patterns of cigar use will allow further assessment of the population health impact of cigars.

Longitudinal pathways of exclusive and polytobacco smokeless use among youth, young adults and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: Use of smokeless tobacco (SLT) with other tobacco products is growing, yet gaps in understanding transitions among SLT and other product use remain. The aim of this study is to examine cross-sectional prevalence and longitudinal pathways of SLT use among US youth (12-17 years), young adults (18-24 years) and adults 25+ (25 years and older). DESIGN: Data were drawn from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth and adults. Respondents with data at all three waves (youth, n=11 046; young adults, n=6478; adults 25+, n=17 188) were included in longitudinal analyses. RESULTS: Young adults had the highest current SLT use compared with other age groups. Among Wave 1 (W1) past 30-day youth and young adult SLT users, most were SLT and cigarette polytobacco users compared with adults 25+, who more often used SLT exclusively. Among W1 exclusive SLT users, persistent exclusive use across all three waves was more common among adults 25+, while transitioning from exclusive SLT use to SLT polytobacco use at Wave 2 or Wave 3 was more common among youth and young adults. Among W1 SLT and cigarette polytobacco users, a common pathway was discontinuing SLT use but continuing other tobacco use. CONCLUSIONS: Our results showed distinct longitudinal transitions among exclusive and SLT polytobacco users. Deeper understanding of these critical product transitions will allow for further assessment of population health impact of these products.

Initiation of any tobacco and five tobacco products across 3 years among youth, young adults and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: This study reports weighted cross-sectional prevalence of never use of tobacco, and longitudinal past 12-month (P12M), past 30-day (P30D) and frequent P30D any tobacco or specific tobacco product initiation across three 1-year waves. Longitudinal three-wave pathways are examined to outline pathways of exclusive and polytobacco initiation, as well as pathways of new initiators of electronic nicotine delivery systems (ENDS) or cigarettes. DESIGN: Data were drawn from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth and adults. Respondents with data at all three waves (youth, N = 11 046; young adults, N = 6478; adults 25+, N = 17 188) were included in longitudinal analyses. RESULTS: Across the three age groups, weighted cross-sectional analyses revealed never any tobacco use decreased each year from 2013 to 2016, reflecting overall increases in tobacco initiation in the population during this time. Compared with cigarettes, cigars, hookah and smokeless tobacco, ENDS had the highest proportion of P12M initiation from Wave 1 to Wave 3 (W3) for each age group. Among youth Wave 2 P30D initiators of exclusive ENDS or cigarettes, the most common W3 outcome was not using any tobacco (ENDS: 59.0% (95% CI 48.4 to 68.8); cigarettes: 40.3% (95% CI 28.7 to 53.1)). CONCLUSIONS: Initiation rates of ENDS among youth and young adults have increased the number of ever tobacco users in the US prevention strategies across the spectrum of tobacco products which can address youth initiation of tobacco products.

Overview of tobacco use transitions for population health.

The Family Smoking Prevention and Tobacco Control Act provided the US Food and Drug Administration authority to regulate tobacco products using a population health standard. Models have been developed to estimate the population health impacts of tobacco initiation, cessation and relapse transitions. Models should be informed by high-quality, longitudinal data to estimate these constructs. Simulation studies have generated data to predict the impact of various tobacco control interventions, including the influence of regulations on tobacco use behaviours and health. The purpose of this paper is to provide a high-level conceptual overview for understanding tobacco transition behaviours and correlates of these behaviours using data from the Population Assessment of Tobacco and Health (PATH) Study, a US nationally representative longitudinal tobacco study of about 46 000 persons aged 12+ years. The papers that follow in this journal issue build and expand on this conceptual overview using data from the first three waves of the PATH Study. These papers describe use patterns of different tobacco products and their correlates, and can serve as foundations for more in-depth papers that will help the research community better understand the population health impacts and drivers of different tobacco use patterns.

Transitions in electronic cigarette use among adults in the Population Assessment of Tobacco and Health (PATH) Study, Waves 1 and 2 (2013-2015).

INTRODUCTION: This study assessed patterns of e-cigarette and cigarette use from Wave 1 to Wave 2 among adult e-cigarette users at Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study. METHODS: We examined changes in e-cigarette use frequency at Wave 2 among adult e-cigarette users at Wave 1 (unweighted n=2835). Adjusted prevalence ratios (aPR) were calculated using a predicted marginal probability approach to assess correlates of e-cigarette discontinuance and smoking abstinence at Wave 2. RESULTS: Half (48.8%) of adult e-cigarette users at Wave 1 discontinued their use of e-cigarettes at Wave 2. Among dual users of e-cigarettes and cigarettes at Wave 1, 44.3% maintained dual use, 43.5% discontinued e-cigarette use and maintained cigarette smoking and 12.1% discontinued cigarette use at Wave 2, either by abstaining from cigarette smoking only (5.1%) or discontinuing both products (7.0%). Among dual users at Wave 1, daily e-cigarette users were more likely than non-daily users to report smoking abstinence at Wave 2 (aPR=1.40, 95% CI 1.02 to 1.91). Using a customisable device (rather than a non-customisable one) was not significantly related to smoking abstinence at Wave 2 (aPR=1.14, 95% CI 0.81 to 1.60). CONCLUSIONS: This study suggests that e-cigarette use patterns are highly variable over a 1-year period. This analysis provides the first nationally representative estimates of transitions among US adult e-cigarette users. Future research, including additional waves of the PATH Study, can provide further insight into long-term patterns of e-cigarette use critical to understanding the net population health impact of e-cigarettes in USA.

e-Cigarette Use Among Youth in the United States, 2019.

Importance: The prevalence of e-cigarette use among US youth increased from 2011 to 2018. Continued monitoring of the prevalence of e-cigarette and other tobacco product use among youth is important to inform public health policy, planning, and regulatory efforts. Objective: To estimate the prevalence of e-cigarette use among US high school and middle school students in 2019 including frequency of use, brands used, and use of flavored products. Design, Setting, and Participants: Cross-sectional analyses of a school-based nationally representative sample of 19 018 US students in grades 6 to 12 participating in the 2019 National Youth Tobacco Survey. The survey was conducted from February 15, 2019, to May 24, 2019. Main Outcomes and Measures: Self-reported current (past 30-day) e-cigarette use estimates among high school and middle school students; frequent use (≥20 days in the past 30 days) and usual e-cigarette brand among current e-cigarette users; and use of flavored e-cigarettes and flavor types among current exclusive e-cigarette users (no use of other tobacco products) by school level and usual brand. Prevalence estimates were weighted to account for the complex sampling design. Results: The survey included 10 097 high school students (mean [SD] age, 16.1 [3.0] years; 47.5% female) and 8837 middle school students (mean [SD] age, 12.7 [2.8] years; 48.7% female). The response rate was 66.3%. An estimated 27.5% (95% CI, 25.3%-29.7%) of high school students and 10.5% (95% CI, 9.4%-11.8%) of middle school students reported current e-cigarette use. Among current e-cigarette users, an estimated 34.2% (95% CI, 31.2%-37.3%) of high school students and 18.0% (95% CI, 15.2%-21.2%) of middle school students reported frequent use, and an estimated 63.6% (95% CI, 59.3%-67.8%) of high school students and 65.4% (95% CI, 60.6%-69.9%) of middle school students reported exclusive use of e-cigarettes. Among current e-cigarette users, an estimated 59.1% (95% CI, 54.8%-63.2%) of high school students and 54.1% (95% CI, 49.1%-59.0%) of middle school students reported JUUL as their usual e-cigarette brand in the past 30 days; among current e-cigarette users, 13.8% (95% CI, 12.0%-15.9%) of high school students and 16.8% (95% CI, 13.6%-20.7%) of middle school students reported not having a usual e-cigarette brand. Among current exclusive e-cigarette users, an estimated 72.2% (95% CI, 69.1%-75.1%) of high school students and 59.2% (95% CI, 54.8%-63.4%) of middle school students used flavored e-cigarettes, with fruit, menthol or mint, and candy, desserts, or other sweets being the most commonly reported flavors. Conclusions and Relevance: In 2019, the prevalence of self-reported e-cigarette use was high among high school and middle school students, with many current e-cigarette users reporting frequent use and most of the exclusive e-cigarette users reporting use of flavored e-cigarettes.

Frequency of Use Among Middle and High School Student Tobacco Product Users - United States, 2015-2017.

Tobacco product use during adolescence increases the risk for lifelong nicotine addiction and immediate adverse health effects (1,2). During 2011-2017, current use of cigarettes, cigars, smokeless tobacco, and pipe tobacco decreased significantly among middle and high school students, but current use of e-cigarettes increased significantly from 1.5% to 11.7% (3). In 2017, an estimated 19.6% of high school students (2.95 million) and 5.6% of middle school students (0.67 million) were current users of any tobacco product; e-cigarettes were the most commonly used tobacco product for both middle (3.3%) and high (11.7%) school students (3). The Food and Drug Administration (FDA) and CDC analyzed combined data from the 2015-2017 National Youth Tobacco Surveys (NYTS) to determine past 30-day (current) frequency of use of cigarettes, e-cigarettes, cigars, smokeless tobacco, and hookahs among U.S. high school and middle school students. During 2015-2017, the proportion of students currently using tobacco products who used a product for ≥20 of the past 30 days ranged from 14.0% of cigar smokers to 38.7% of smokeless tobacco users among high school students and from 13.1% of e-cigarette users to 24.5% of hookah smokers among middle school students. Among current users, use of two or more tobacco products ranged from 76.7% (e-cigarettes) to 90.9% (hookahs) among those using the product ≥20 of the preceding 30 days, from 68.0% (e-cigarettes) to 84.2% (hookahs) among those using the product for 6 to 19 of the preceding 30 days, and from 48.8% (e-cigarettes) to 77.2% (cigarettes) among those using the product for 1 to 5 of the preceding 30 days. Sustained implementation of proven tobacco control strategies focusing on all types of tobacco products, in coordination with the regulation of tobacco products by FDA, are needed to reduce tobacco product initiation and use among U.S. youths.

Association between serum 25-hydroxyvitamin D and serum sex steroid hormones among men in NHANES.

BACKGROUND: Recent literature suggests that high circulating vitamin D may increase prostate cancer risk. Although the mechanism through which vitamin D may increase risk is unknown, vitamin D concentration could influence circulating sex steroid hormones that may be associated with prostate cancer; an alternate explanation is that it could be associated with prostate-specific antigen (PSA) concentration causing detection bias. OBJECTIVE: We examined whether serum vitamin D concentration was associated with sex steroid hormone and PSA concentrations in a cross-sectional analysis of men in the National Health and Nutrition Examination Surveys (NHANES). DESIGN: Testosterone, oestradiol, sex hormone-binding globulin (SHBG), androstanediol glucuronide, and 25-hydroxyvitamin D (25(OH)D) were measured in serum from men aged 20 and older participating in NHANES III (n = 1315) and NHANES 2001-2004 (n = 318). Hormone concentrations were compared across 25(OH)D quintiles, adjusting for age, race/ethnicity, body fat percentage, and smoking. PSA concentration was estimated by 25(OH)D quintile in 4013 men from NHANES 2001-2006. RESULTS: In NHANES III, higher testosterone (quintile (Q) 1 = 17·2, 95% confidence interval (CI) = 16·1-18·6; Q5 = 19·6, 95% CI = 18·7-20·6 nmol/l, P-trend = 0·0002) and SHBG (Q1 = 33·8, 95% CI = 30·8-37·0; Q5 = 38·4, 95% CI = 35·8-41·2 nmol/l, P-trend = 0·0005) were observed with increasing 25(OH)D. Similar results were observed in NHANES 2001-2004. PSA concentration was not associated with serum 25(OH)D (P-trend = 0·34). CONCLUSION: Results from these nationally representative studies support a positive association between serum 25(OH)D and testosterone and SHBG. The findings support an indirect mechanism through which vitamin D may increase prostate cancer risk, and suggest the link to prostate cancer is not due to PSA-detection bias.

Analgesic use and the risk of primary adult brain tumor.

Glioma and meningioma are uncommon tumors of the brain with few known risk factors. Regular use of aspirin has been linked to a lower risk of gastrointestinal and other cancers, though evidence for an association with brain tumors is mixed. We examined the association of aspirin and other analgesics with the risk of glioma and meningioma in a large US case-control study. Cases were persons recently diagnosed with glioma or meningioma and treated at medical centers in the southeastern US. Controls were persons sampled from the same communities as the cases combined with friends and other associates of the cases. Information on past use of analgesics (aspirin, other anti-inflammatory agents, and acetaminophen) was collected in structured interviews. Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for analgesic use adjusted for potential confounders. All associations were considered according to indication for use. A total of 1123 glioma cases, 310 meningioma cases and 1296 controls were included in the analysis. For indications other than headache, glioma cases were less likely than controls to report regular use of aspirin (OR 0.69; CI 0.56, 0.87), in a dose-dependent manner (P trend < 0.001). No significant associations were observed with other analgesics for glioma, or any class of pain reliever for meningioma. Results suggest that regular aspirin use may reduce incidence of glioma.

Inherited variation in the PARP1 gene and survival from melanoma.

We report the association of an inherited variant located upstream of the poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single-strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting for factors known to be associated with survival. Survival was measured as overall survival (OS) and, where available, melanoma-specific survival (MSS). Results were combined using random effects meta-analysis. Evidence for a role of the PARP1 protein in melanoma ulceration and survival was investigated by testing gene expression levels taken from formalin-fixed paraffin-embedded tumors. A significant association was seen for inheritance of the rarer variant of PARP1, rs2249844 with OS (hazard ratio (HR) = 1.16 per allele, 95% confidence interval (CI) 1.04-1.28, p = 0.005, eleven cohorts) and MSS (HR = 1.20 per allele, 95% CI 1.01-1.39, p = 0.03, eight cohorts). We report bioinformatic data supportive of a functional effect for rs2249844. Higher levels of PARP1 gene expression in tumors were shown to be associated with tumor ulceration and poorer OS.

Circadian pathway genes in relation to glioma risk and outcome.

PURPOSE: There is growing evidence that circadian disruption may alter risk and aggressiveness of cancer. We evaluated common genetic variants in the circadian gene pathway for associations with glioma risk and patient outcome in a US clinic-based case-control study. METHODS: Subjects were genotyped for 17 candidate single nucleotide polymorphisms in ARNTL, CRY1, CRY2, CSNK1E, KLHL30, NPAS2, PER1, PER3, CLOCK, and MYRIP. Unconditional logistic regression was used to estimate age and gender-adjusted odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk under three inheritance models (additive, dominant, and recessive). Proportional hazards regression was used to estimate hazard ratios for glioma-related death among 441 patients with high-grade tumors. Survival associations were validated using The Cancer Genome Atlas (TCGA) dataset. RESULTS: A variant in PER1 (rs2289591) was significantly associated with overall glioma risk (per variant allele OR 0.80; 95 % CI 0.66-0.97; p trend = 0.027). The variant allele for CLOCK rs11133391 under a recessive model increased risk of oligodendroglioma (OR 2.41; 95 % CI 1.31-4.42; p = 0.005), though not other glioma subtypes (p for heterogeneity = 0.0033). The association remained significant after false discovery rate adjustment (p = 0.008). Differential associations by gender were observed for MYRIP rs6599077 and CSNK1E rs1534891 though differences were not significant after adjustment for multiple testing. No consistent mortality associations were identified. Several of the examined genes exhibited differential expression in glioblastoma multiforme versus normal brain in TCGA data (MYRIP, ARNTL, CRY1, KLHL30, PER1, CLOCK, and PER3), and expression of NPAS2 was significantly associated with a poor patient outcome in TCGA patients. CONCLUSION: This exploratory analysis provides some evidence supporting a role for circadian genes in the onset of glioma and possibly the outcome of glioma.

Reproductive factors and risk of primary brain tumors in women.

Gender-specific incidence patterns and the presence of hormonal receptors on tumor cells suggest that sex hormones may play a role in the onset of primary brain tumors. However, epidemiological studies on the relation of hormonal risk factors to the risk of brain tumors have been inconsistent. We examined the role of reproductive factors in the onset of glioma and meningioma in a case-control study conducted in the Southeastern US that included 507 glioma cases, 247 meningioma cases, and 695 community-based and friend controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) adjusting for age, race, US state of residence, and education. An older age at menarche was associated with an increased risk of glioma (≥ 15 vs. ≤ 12 years: OR 1.65; 95% CI 1.11-2.45), with a stronger association observed in pre-menopausal (OR 2.22; 95% CI 1.12-4.39) than post-menopausal (OR 1.55; 95% CI 0.93-2.58) women. When compared to controls, meningioma cases were more likely to have undergone natural menopause (OR 1.52; 95% CI 1.04-2.21) whereas glioma cases were less likely to be long term users of oral contraceptives (OR 0.47; 95% CI 0.33-0.68). Increasing parity was not related to the risk of either tumor. Current findings are consistent with a limited role for hormones in the onset of brain tumors in women. Results contribute to a growing body of evidence that a later age at menarche increases the risk of glioma in women.

Toenail iron, genetic determinants of iron status, and the risk of glioma.

PURPOSE: Iron is essential for oxygen transport and oxidative metabolism; however, elevated iron stores can trigger overproduction of reactive oxygen species and induce DNA damage. Little is known about the association between body iron stores and glioma risk. This study examined the associations of iron levels measured in toenails and genetic variants linked to body iron stores with risk of glioma in a clinic-based case-control study. METHODS: Samples were collected a median of 24 days following glioma diagnosis in the cases (10th-90th percentile, range: 10-44 days). Nail iron levels were measured in 300 cases and 300 controls using neutron activation analysis. A total of 24 genetic variants associated with iron status were genotyped in 622 cases and 628 controls. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk according to toenail iron and the examined genotypes. RESULTS: No association was observed between toenail iron and glioma risk when restricting to cases with nails collected within ~3 weeks of diagnosis (OR = 0.93; 95 % CI 0.46, 1.87 comparing those with high (≥14 µg/g) vs. low (<6 µg/g) iron levels). In contrast, an inverse association with increasing iron was observed after restricting to cases with a delay of 3 weeks or greater (OR = 0.42; 95 % CI 0.19, 0.95), reflecting potentially insidious effects of advancing disease on iron levels among the cases. No associations were observed for any of the examined genetic variants. CONCLUSION: The results do not support a role for body iron stores as a determinant of glioma risk.