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1.
J Natl Cancer Inst ; 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33484569

RESUMO

BACKGROUND: Guidelines recommend offering cessation to smokers eligible for lung cancer screening but there is little data comparing specific cessation approaches in this setting. We compared the benefits and costs of different smoking cessation interventions to help screening programs select specific cessation approaches. METHODS: We conducted a societal-perspective cost-effectiveness analysis using a Cancer Intervention and Surveillance Modeling Network (CISNET) model simulating individuals born in 1960 over their lifetimes. Model inputs were derived from Medicare, national cancer registries, published studies, and micro-costing of cessation interventions. We modeled annual lung cancer screening following 2014 US Preventive Services Task Force guidelines +/- cessation interventions offered to current smokers at first screen, including pharmacotherapy only or pharmacotherapy with electronic/web-based, telephone, individual, or group counseling. Outcomes included lung cancer cases and deaths, life-years saved (LYS), quality-adjusted life-years saved (QALYs), costs, and incremental cost-effectiveness ratios. RESULTS: Compared to screening alone, all cessation interventions decreased cases of and deaths from lung cancer. Compared incrementally, efficient cessation strategies included pharmacotherapy with either web-based cessation ($555 per QALY), telephone counseling ($7,562 per QALY), or individual counseling ($35,531 per QALY). Cessation continued to have costs per QALY well below accepted willingness to pay thresholds even with the lowest intervention effects and was more cost-effective in cohorts with higher smoking prevalence. CONCLUSION: All smoking cessation interventions delivered with lung cancer screening are likely to provide benefits at reasonable costs. Since the differences between approaches were small, the choice of intervention should be guided by practical concerns such as staff training and availability.

2.
Tob Control ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199541

RESUMO

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

3.
Am J Health Promot ; : 890117120964065, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33047619

RESUMO

PURPOSE: To provide tobacco product use patterns for US adults by sociodemographic group. DESIGN: A secondary analysis of Tobacco Use Supplement to the Current Population Survey (2014-15), National Health Interview Survey (2015), and Population Assessment of Tobacco and Health (2015-16). SETTING: United States. SAMPLE: Three nationally representative samples of adults (N = 28,070-155,067). MEASURES: All possible combinations of cigarette, Electronic Nicotine Delivery Systems (ENDS), other combustible product, and smokeless tobacco use, defined as current use every day or some days. ANALYSIS: Weighted population prevalence and proportion among tobacco users of exclusive, dual, and polyuse patterns by sex, race/ethnicity, education, income, and age. RESULTS: Exclusive cigarette use was the most prevalent pattern (10.9-12.8% of US population). Dual and polyuse were less prevalent at the population level (2.6-5.2% and 0.3-1.3%, respectively) but represented 16.7-25.5% of product use among tobacco users. Cigarette plus ENDS use was similar by sex, but men were more likely to be dual users of cigarettes plus other combustibles or smokeless tobacco. Among race/ethnic subgroups, non-Hispanic (NH) Whites were most likely to use cigarettes plus ENDS, while NH Blacks were most likely to use cigarettes plus other combustibles. Dual and polyuse were generally less common among adults with higher education, income, and age. CONCLUSION: Differences in product use patterns by sociodemographic group likely represent different risk profiles with important implications for resulting health disparities.

5.
J Thorac Oncol ; 15(7): 1160-1169, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32160967

RESUMO

INTRODUCTION: Annual lung cancer screening with low-dose computed tomography is recommended for adults aged 55 to 80 years with a greater than or equal to 30 pack-year smoking history who currently smoke or quit within the past 15 years. The 50% who are current smokers should be offered cessation interventions, but information about the impact of adding cessation to screening is limited. METHODS: We used an established lung cancer simulation model to compare the effects on mortality of a hypothetical one-time cessation intervention and annual screening versus annual screening only among screen-eligible individuals born in 1950 or 1960. Model inputs were derived from national data and included smoking history, probability of quitting with and without intervention, lung cancer risk and treatment effectiveness, and competing tobacco-related mortality. We tested the sensitivity of results under different assumptions about screening use and cessation efficacy. RESULTS: Smoking cessation reduces lung cancer mortality and delays overall deaths versus screening only across all assumptions. For example, if screening was used by 30% of screen-eligible individuals born in 1950, adding an intervention with a 10% quit probability reduces lung cancer deaths by 14% and increases life years gained by 81% compared with screening alone. The magnitude of cessation benefits varied under screening uptake rates, cessation effectiveness, and birth cohort. CONCLUSIONS: Smoking cessation interventions have the potential to greatly enhance the impact of lung cancer screening programs. Evaluation of specific interventions, including costs and feasibility of implementation and dissemination, is needed to determine the best possible strategies and realize the full promise of lung cancer screening.

6.
J Natl Cancer Inst ; 112(11): 1136-1142, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32040195

RESUMO

BACKGROUND: Current US Preventive Services Task Force (USPSTF) lung cancer screening guidelines are based on smoking history and age (55-80 years). These guidelines may miss those at higher risk, even at lower exposures of smoking or younger ages, because of other risk factors such as race, family history, or comorbidity. In this study, we characterized the demographic and clinical profiles of those selected by risk-based screening criteria but were missed by USPSTF guidelines in younger (50-54 years) and older (71-80 years) age groups. METHODS: We used data from the National Health Interview Survey, the CISNET Smoking History Generator, and results of logistic prediction models to simulate lifetime lung cancer risk-factor data for 100 000 individuals in the 1950-1960 birth cohorts. We calculated age-specific 6-year lung cancer risk for each individual from ages 50 to 90 years using the PLCOm2012 model and evaluated age-specific screening eligibility by USPSTF guidelines and by risk-based criteria (varying thresholds between 1.3% and 2.5%). RESULTS: In the 1950 birth cohort, 5.4% would have been ineligible for screening by USPSTF criteria in their younger ages but eligible based on risk-based criteria. Similarly, 10.4% of the cohort would be ineligible for screening by USPSTF in older ages. Notably, high proportions of blacks were ineligible for screening by USPSTF criteria at younger (15.6%) and older (14.2%) ages, which were statistically significantly greater than those of whites (4.8% and 10.8%, respectively; P < .001). Similar results were observed with other risk thresholds and for the 1960 cohort. CONCLUSIONS: Further consideration is needed to incorporate comprehensive risk factors, including race and ethnicity, into lung cancer screening to reduce potential racial disparities.

7.
J Natl Cancer Inst ; 112(5): 466-479, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31566216

RESUMO

BACKGROUND: Risk-prediction models have been proposed to select individuals for lung cancer screening. However, their long-term effects are uncertain. This study evaluates long-term benefits and harms of risk-based screening compared with current United States Preventive Services Task Force (USPSTF) recommendations. METHODS: Four independent natural history models were used to perform a comparative modeling study evaluating long-term benefits and harms of selecting individuals for lung cancer screening through risk-prediction models. In total, 363 risk-based screening strategies varying by screening starting and stopping age, risk-prediction model used for eligibility (Bach, PLCOm2012, or Lung Cancer Death Risk Assessment Tool [LCDRAT]), and risk threshold were evaluated for a 1950 US birth cohort. Among the evaluated outcomes were percentage of individuals ever screened, screens required, lung cancer deaths averted, life-years gained, and overdiagnosis. RESULTS: Risk-based screening strategies requiring similar screens among individuals ages 55-80 years as the USPSTF criteria (corresponding risk thresholds: Bach = 2.8%; PLCOm2012 = 1.7%; LCDRAT = 1.7%) averted considerably more lung cancer deaths (Bach = 693; PLCOm2012 = 698; LCDRAT = 696; USPSTF = 613). However, life-years gained were only modestly higher (Bach = 8660; PLCOm2012 = 8862; LCDRAT = 8631; USPSTF = 8590), and risk-based strategies had more overdiagnosed cases (Bach = 149; PLCOm2012 = 147; LCDRAT = 150; USPSTF = 115). Sensitivity analyses suggest excluding individuals with limited life expectancies (<5 years) from screening retains the life-years gained by risk-based screening, while reducing overdiagnosis by more than 65.3%. CONCLUSIONS: Risk-based lung cancer screening strategies prevent considerably more lung cancer deaths than current recommendations do. However, they yield modest additional life-years and increased overdiagnosis because of predominantly selecting older individuals. Efficient implementation of risk-based lung cancer screening requires careful consideration of life expectancy for determining optimal individual stopping ages.

8.
Gastroenterology ; 158(5): 1274-1286.e12, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31866242

RESUMO

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Idade de Início , Estudos de Casos e Controles , Estudos de Coortes , Análise Mutacional de DNA , Conjuntos de Dados como Assunto , Feminino , Estudo de Associação Genômica Ampla , Técnicas de Genotipagem , Humanos , Estilo de Vida , Masculino , Anamnese , Pessoa de Meia-Idade , Taxa de Mutação , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Sequenciamento Completo do Genoma
9.
BMJ Open Gastroenterol ; 6(1): e000339, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31875139

RESUMO

Objective: 'Environmental' factors associated with colorectal cancer (CRC) risk include modifiable and non-modifiable variables. Whether those with different non-modifiable baseline risks will benefit similarly from reducing their modifiable CRC risks remains unclear. Design: Using 7945 cases and 8893 controls from 11 population-based studies, we combined 17 risk factors to characterise the overall environmental predisposition to CRC (environmental risk score (E-score)). We estimated the absolute risks (ARs) of CRC of 10 and 30 years across E-score using incidence-rate data from the Surveillance, Epidemiology, and End Results programme. We then combined the modifiable risk factors and estimated ARs across the modifiable risk score, stratified by non-modifiable risk profile based on genetic predisposition, family history and height. Results: Higher E-score was associated with increased CRC risk (ORquartile, 1.33; 95% CI 1.30 to 1.37). Across E-scores, 30-year ARs of CRC increased from 2.5% in the lowest quartile (Q1) to 5.9% in the highest (Q4) quartile for men, and from 2.1% to 4.5% for women. The modifiable risk score had a stronger association in those with high non-modifiable risk (relative excess risk due to interaction=1.2, 95% CI 0.5 to 1.9). For those in Q4 of non-modifiable risk, a decrease in modifiable risk reduced 30-year ARs from 8.9% to 3.4% for men and from 6.0% to 3.2% for women, a level lower or comparable to the average population risk. Conclusions: Changes in modifiable risk factors may result in a substantial decline in CRC risk in both sexes. Those with high inherited risk may reap greater benefit from lifestyle modifications. Our results suggested comprehensive evaluation of environmental factors may facilitate CRC risk stratification.

10.
Ann Intern Med ; 171(11): 796-804, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31683314

RESUMO

Background: Recommendations vary regarding the maximum age at which to stop lung cancer screening: 80 years according to the U.S. Preventive Services Task Force (USPSTF), 77 years according to the Centers for Medicare & Medicaid Services (CMS), and 74 years according to the National Lung Screening Trial (NLST). Objective: To compare the cost-effectiveness of different stopping ages for lung cancer screening. Design: By using shared inputs for smoking behavior, costs, and quality of life, 4 independently developed microsimulation models evaluated the health and cost outcomes of annual lung cancer screening with low-dose computed tomography (LDCT). Data Sources: The NLST; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; SEER (Surveillance, Epidemiology, and End Results) program; Nurses' Health Study and Health Professionals Follow-up Study; and U.S. Smoking History Generator. Target Population: Current, former, and never-smokers aged 45 years from the 1960 U.S. birth cohort. Time Horizon: 45 years. Perspective: Health care sector. Intervention: Annual LDCT according to NLST, CMS, and USPSTF criteria. Outcome Measures: Incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY). Results of Base-Case Analysis: The 4 models showed that the NLST, CMS, and USPSTF screening strategies were cost-effective, with ICERs averaging $49 200, $68 600, and $96 700 per QALY, respectively. Increasing the age at which to stop screening resulted in a greater reduction in mortality but also led to higher costs and overdiagnosis rates. Results of Sensitivity Analysis: Probabilistic sensitivity analysis showed that the NLST and CMS strategies had higher probabilities of being cost-effective (98% and 77%, respectively) than the USPSTF strategy (52%). Limitation: Scenarios assumed 100% screening adherence, and models extrapolated beyond clinical trial data. Conclusion: All 3 sets of lung cancer screening criteria represent cost-effective programs. Despite underlying uncertainty, the NLST and CMS screening strategies have high probabilities of being cost-effective. Primary Funding Source: CISNET (Cancer Intervention and Surveillance Modeling Network) Lung Group, National Cancer Institute.


Assuntos
Análise Custo-Benefício , Detecção Precoce de Câncer/economia , Neoplasias Pulmonares/diagnóstico , Programas de Rastreamento/economia , Modelos Estatísticos , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer/métodos , Humanos , Neoplasias Pulmonares/epidemiologia , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Qualidade de Vida , Fatores de Risco , Sensibilidade e Especificidade , Fumar/efeitos adversos , Tomografia Computadorizada por Raios X/economia , Estados Unidos/epidemiologia
11.
Cancer Causes Control ; 30(12): 1377-1388, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606852

RESUMO

PURPOSE: Liver cancer incidence continues to increase while incidence of most other cancers is decreasing. We analyze recent and long-term trends of US liver cancer incidence by race/ethnicity and sex to best understand where to focus preventive efforts. METHODS: Liver cancer incidence rates from 1992 to 2016 were obtained from the Surveillance, Epidemiology, and End Results registry. Delay-adjusted age-standardized incidence trends by race/ethnicity and sex were analyzed using joinpoint regression. Age-specific incidence was analyzed using age-period-cohort models. Hepatitis C seroprevalence by cohort was calculated using National Health and Nutrition Examination Survey data. RESULTS: Liver cancer incidence has peaked in males and Asian or Pacific Islanders. Hispanic males, a high-incidence population, are experiencing a decrease in incidence, although not yet statistically significant. In contrast, incidence continues to increase in females, although at lower rates than in the 1990s, and American Indian/Alaska Natives (AI/ANs). Liver cancer incidence continues to be higher in males. Non-Hispanic Whites have the lowest incidence among racial/ethnic groups. Trends largely reflect differences in incidence by birth-cohort, which increased considerably, particularly in males, for those born around the 1950s, and continues to increase in females and AI/ANs. The patterns in males are likely driven by cohort variations in Hepatitis C infection. CONCLUSIONS: Liver cancer incidence appears to have peaked among males. However, important differences in liver cancer trends by race/ethnicity and sex remain, highlighting the need for monitoring trends across different groups. Preventive interventions should focus on existing liver cancer disparities, targeting AI/ANs, females, and high-incidence groups.


Assuntos
Grupos de Populações Continentais/estatística & dados numéricos , Grupos Étnicos/estatística & dados numéricos , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Sistema de Registros/estatística & dados numéricos , Estudos Soroepidemiológicos , Estados Unidos/epidemiologia , Adulto Jovem
12.
Lung Cancer ; 135: 205-216, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31446996

RESUMO

OBJECTIVES: Current guidelines recommend delivery of smoking cessation interventions with lung cancer screening (LCS). Unfortunately, there are limited data to guide clinicians and policy-makers in choosing cessation interventions in this setting. Several trials are underway to fill this evidence gap, but results are not expected for several years. METHODS AND MATERIALS: We conducted a systematic review and meta-analysis of current literature on the efficacy of smoking cessation interventions among populations eligible for LCS. We searched PubMed, Medline, and PsycINFO for randomized controlled trials of smoking cessation interventions published from 2010-2017. Trials were eligible for inclusion if they sampled individuals likely to be eligible for LCS based on age and smoking history, had sample sizes >100, follow-up of 6- or 12-months, and were based in North America, Western Europe, Australia, or New Zealand. RESULTS: Three investigators independently screened 3,813 abstracts and identified 332 for full-text review. Of these, 85 trials were included and grouped into categories based on the primary intervention: electronic/web-based, in-person counseling, pharmacotherapy, and telephone counseling. At 6-month follow-up, electronic/web-based (odds ratio [OR] 1.14, 95% CI 1.03-1.25), in-person counseling (OR 1.46, 95% CI 1.25-1.70), and pharmacotherapy (OR 1.53, 95% CI 1.33-1.77) interventions significantly increased the odds of abstinence. Telephone counseling increased the odds but did not reach statistical significance (OR 1.21, 95% CI 0.98-1.50). At 12-months, in-person counseling (OR 1.28 95% CI 1.10-1.50) and pharmacotherapy (OR 1.46, 95% CI 1.17-1.84) remained efficacious, although the decrement in efficacy was of similar magnitude across all intervention categories. CONCLUSIONS: Several categories of cessation interventions are promising for implementation in the LCS setting.


Assuntos
Aconselhamento , Intervenção Educacional Precoce , Neoplasias Pulmonares/epidemiologia , Abandono do Hábito de Fumar , Humanos , Neoplasias Pulmonares/etiologia , Programas de Rastreamento , Razão de Chances , Viés de Publicação
13.
JAMA Netw Open ; 2(3): e190204, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30821827

RESUMO

Importance: Low-dose computed tomography lung cancer screening is most effective when applied to high-risk individuals. Objectives: To develop and validate a risk prediction model that incorporates low-dose computed tomography screening results. Design, Setting, and Participants: A logistic regression risk model was developed in National Lung Screening Trial (NLST) Lung Screening Study (LSS) data and was validated in NLST American College of Radiology Imaging Network (ACRIN) data. The NLST was a randomized clinical trial that recruited participants between August 2002 and April 2004, with follow-up to December 31, 2009. This secondary analysis of data from the NLST took place between August 10, 2013, and November 1, 2018. Included were LSS (n = 14 576) and ACRIN (n = 7653) participants who had 3 screens, adequate follow-up, and complete predictor information. Main Outcomes and Measures: Incident lung cancers occurring 1 to 4 years after the third screen (202 LSS and 96 ACRIN). Predictors included scores from the validated PLCOm2012 risk model and Lung CT Screening Reporting & Data System (Lung-RADS) screening results. Results: Overall, the mean (SD) age of 22 229 participants was 61.3 (5.0) years, 59.3% were male, and 90.9% were of non-Hispanic white race/ethnicity. During follow-up, 298 lung cancers were diagnosed in 22 229 individuals (1.3%). Eight result combinations were pooled into 4 groups based on similar associations. Adjusted for PLCOm2012 risks, compared with participants with 3 negative screens, participants with 1 positive screen and last negative had an odds ratio (OR) of 1.93 (95% CI, 1.34-2.76), and participants with 2 positive screens with last negative or 2 negative screens with last positive had an OR of 2.66 (95% CI, 1.60-4.43); when 2 or more screens were positive with last positive, the OR was 8.97 (95% CI, 5.76-13.97). In ACRIN validation data, the model that included PLCOm2012 scores and screening results (PLCO2012results) demonstrated significantly greater discrimination (area under the curve, 0.761; 95% CI, 0.716-0.799) than when screening results were excluded (PLCOm2012) (area under the curve, 0.687; 95% CI, 0.645-0.728) (P < .001). In ACRIN validation data, PLCO2012results demonstrated good calibration. Individuals who had initial negative scans but elevated PLCOm2012 six-year risks of at least 2.6% did not have risks decline below the 1.5% screening eligibility criterion when subsequent screens were negative. Conclusions and Relevance: According to this analysis, some individuals with elevated risk scores who have negative initial screens remain at elevated risks, warranting annual screening. Positive screens seem to increase baseline risk scores and may identify high-risk individuals for continued screening and enrollment into clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT00047385.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Medição de Risco , Tomografia Computadorizada por Raios X/métodos , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Reprodutibilidade dos Testes , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco
14.
Nat Genet ; 51(1): 76-87, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30510241

RESUMO

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Fatores de Risco , Transdução de Sinais/genética
15.
Ann Intern Med ; 169(10): 684-693, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30304504

RESUMO

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


Assuntos
Neoplasias Pulmonares/mortalidade , Fumar/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Feminino , Humanos , Expectativa de Vida , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/prevenção & controle , Masculino , Pessoa de Meia-Idade , Prevalência , Fumar/epidemiologia , Fumar/tendências , Abandono do Hábito de Fumar , Estados Unidos/epidemiologia
16.
J Glob Oncol ; 4: 1-29, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30192698

RESUMO

Purpose Lung cancer is one of the most common cancers worldwide and in Thailand. We characterize and forecast region-specific patterns of lung cancer incidence by histology and sex. Methods We analyzed lung cancer incidence trends in Thailand by histology (adenocarcinoma [AdC]; squamous cell carcinoma [SCC]; and large-cell, small-cell, and other carcinomas) from 1990 to 2014 in four cancer registries in three regions (north, Chiang Mai Province and Lampang Province; northeast: Khon Kaen Province; south: Songkhla Province). Annual percent change (APC) was calculated to quantify the incidence rate trends using joinpoint regression. Age-period-cohort models were used to examine the temporal trends of AdC and SCC by age, calendar year, and birth cohort. We projected the incidence of AdC and SCC up to 2030 using three independent approaches: joinpoint, age-period-cohort, and Nordpred models. Results AdC incidence significantly increased from 1990 to 2012 in Chiang Mai males (APC, 1.3%), Songkhla males from 2004 to 2014 (APC, 2.5%), Songkhla females from 1990 to 2014 (APC, 5.9%), and Khon Kaen females from 2005 to 2014 (APC, 3.1%). Conversely, SCC incidence significantly decreased from 1990 to 2012 in Chiang Mai males and females (APC, -1.2% and -4.8%, respectively), Lampang males and females from 1993 to 2014 (APC, -5.4% and -5.2%, respectively), and Songkhla females from 1990 to 2014 (APC, -2.1%). In general, trends of AdC and SCC correlated more with birth cohort than with calendar year. Three projection models suggested that incidence rates of AdC in Songkhla may continue to increase until 2030. Conclusion Temporal trends of lung cancer by histology varied among regions in Thailand. Reduction of lung cancer incidence in Thailand likely will require prevention strategies tailored to each specific region.


Assuntos
Neoplasias Pulmonares/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Tailândia/epidemiologia
17.
BMJ Open ; 8(3): e019169, 2018 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-29574440

RESUMO

INTRODUCTION: Smoking remains the leading cause of preventable death in the USA but can be reduced through policy interventions. Computational models of smoking can provide estimates of the projected impact of tobacco control policies and can be used to inform public health decision making. We outline a protocol for simulating the effects of tobacco policies on population health outcomes. METHODS AND ANALYSIS: We extend the Smoking History Generator (SHG), a microsimulation model based on data from the National Health Interview Surveys, to evaluate the effects of tobacco control policies on projections of smoking prevalence and mortality in the USA. The SHG simulates individual life trajectories including smoking initiation, cessation and mortality. We illustrate the application of the SHG policy module for four types of tobacco control policies at the national and state levels: smoke-free air laws, cigarette taxes, increasing tobacco control programme expenditures and raising the minimum age of legal access to tobacco. Smoking initiation and cessation rates are modified by age, birth cohort, gender and years since policy implementation. Initiation and cessation rate modifiers are adjusted for differences across age groups and the level of existing policy coverage. Smoking prevalence, the number of population deaths avoided, and life-years gained are calculated for each policy scenario at the national and state levels. The model only considers direct individual benefits through reduced smoking and does not consider benefits through reduced exposure to secondhand smoke. ETHICS AND DISSEMINATION: A web-based interface is being developed to integrate the results of the simulations into a format that allows the user to explore the projected effects of tobacco control policies in the USA. Usability testing is being conducted in which experts provide feedback on the interface. Development of this tool is under way, and a publicly accessible website is available at http://www.tobaccopolicyeffects.org.


Assuntos
Simulação por Computador , Política Antifumo/legislação & jurisprudência , Abandono do Hábito de Fumar/estatística & dados numéricos , Prevenção do Hábito de Fumar/economia , Fumar/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Saúde Pública , Projetos de Pesquisa , Fumar/tendências , Prevenção do Hábito de Fumar/métodos , Impostos/legislação & jurisprudência , Estados Unidos/epidemiologia , Adulto Jovem
18.
Gastroenterology ; 154(8): 2152-2164.e19, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29458155

RESUMO

BACKGROUND & AIMS: Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening. METHODS: We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005. Half of the participants were used to develop the risk determination model and the other half were used to evaluate the discriminatory accuracy (validation set). Models of CRC risk were created based on family history, 19 lifestyle and environmental factors (E-score), and 63 CRC-associated single-nucleotide polymorphisms identified in genome-wide association studies (G-score). We evaluated the discriminatory accuracy of the models by calculating area under the receiver operating characteristic curve values, adjusting for study, age, and endoscopy history for the validation set. We used the models to project the 10-year absolute risk of CRC for a given risk profile and recommend ages to begin screening in comparison to CRC risk for an average individual at 50 years of age, using external population incidence rates for non-Hispanic whites from the Surveillance, Epidemiology, and End Results program registry. RESULTS: In our models, E-score and G-score each determined risk of CRC with greater accuracy than family history. A model that combined both scores and family history estimated CRC risk with an area under the receiver operating characteristic curve value of 0.63 (95% confidence interval, 0.62-0.64) for men and 0.62 (95% confidence interval, 0.61-0.63) for women; area under the receiver operating characteristic curve values based on only family history ranged from 0.53 to 0.54 and those based only E-score or G-score ranged from 0.59 to 0.60. Although screening is recommended to begin at age 50 years for individuals with no family history of CRC, starting ages calculated based on combined E-score and G-score differed by 12 years for men and 14 for women, for individuals with the highest vs the lowest 10% of risk. CONCLUSIONS: We used data from 2 large international consortia to develop CRC risk calculation models that included genetic and environmental factors along with family history. These determine risk of CRC and starting ages for screening with greater accuracy than the family history only model, which is based on the current screening guideline. These scoring systems might serve as a first step toward developing individualized CRC prevention strategies.


Assuntos
Colonoscopia/normas , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/normas , Modelos Biológicos , Fatores Etários , Idoso , Neoplasias Colorretais/genética , Detecção Precoce de Câncer/métodos , Meio Ambiente , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Guias de Prática Clínica como Assunto , Curva ROC , Medição de Risco/métodos , Fatores Sexuais
20.
PLoS Med ; 14(4): e1002277, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28376113

RESUMO

BACKGROUND: Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years). Nine previously established risk models were assessed for their ability to identify those most likely to develop or die from lung cancer. All models considered age and various aspects of smoking exposure (smoking status, smoking duration, cigarettes per day, pack-years smoked, time since smoking cessation) as risk predictors. In addition, some models considered factors such as gender, race, ethnicity, education, body mass index, chronic obstructive pulmonary disease, emphysema, personal history of cancer, personal history of pneumonia, and family history of lung cancer. METHODS AND FINDINGS: Retrospective analyses were performed on 53,452 National Lung Screening Trial (NLST) participants (1,925 lung cancer cases and 884 lung cancer deaths) and 80,672 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) ever-smoking participants (1,463 lung cancer cases and 915 lung cancer deaths). Six-year lung cancer incidence and mortality risk predictions were assessed for (1) calibration (graphically) by comparing the agreement between the predicted and the observed risks, (2) discrimination (area under the receiver operating characteristic curve [AUC]) between individuals with and without lung cancer (death), and (3) clinical usefulness (net benefit in decision curve analysis) by identifying risk thresholds at which applying risk-based eligibility would improve lung cancer screening efficacy. To further assess performance, risk model sensitivities and specificities in the PLCO were compared to those based on the NLST eligibility criteria. Calibration was satisfactory, but discrimination ranged widely (AUCs from 0.61 to 0.81). The models outperformed the NLST eligibility criteria over a substantial range of risk thresholds in decision curve analysis, with a higher sensitivity for all models and a slightly higher specificity for some models. The PLCOm2012, Bach, and Two-Stage Clonal Expansion incidence models had the best overall performance, with AUCs >0.68 in the NLST and >0.77 in the PLCO. These three models had the highest sensitivity and specificity for predicting 6-y lung cancer incidence in the PLCO chest radiography arm, with sensitivities >79.8% and specificities >62.3%. In contrast, the NLST eligibility criteria yielded a sensitivity of 71.4% and a specificity of 62.2%. Limitations of this study include the lack of identification of optimal risk thresholds, as this requires additional information on the long-term benefits (e.g., life-years gained and mortality reduction) and harms (e.g., overdiagnosis) of risk-based screening strategies using these models. In addition, information on some predictor variables included in the risk prediction models was not available. CONCLUSIONS: Selection of individuals for lung cancer screening using individual risk is superior to selection criteria based on age and pack-years alone. The benefits, harms, and feasibility of implementing lung cancer screening policies based on risk prediction models should be assessed and compared with those of current recommendations.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Modelos Teóricos , Seleção de Pacientes , Idoso , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
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