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1.
Ann Am Thorac Soc ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400907

RESUMO

RATIONALE: A prospective longitudinal cohort of individuals at high-risk of developing lung cancer was established to build a biorepository of carefully annotated biological specimens and low-dose computed tomography (LDCT) chest images for derivation and validation of candidate biomarkers for early detection of lung cancer. OBJECTIVE: The goal of this study is to characterize individuals with high-risk for lung cancer, accumulating valuable biospecimens and LDCT chest scan longitudinally over five years. METHODS: Participants 55-80 years of age and with a 5-year estimated risk of developing lung cancer greater than 1.5% were recruited and enrolled from clinics at Vanderbilt University Medical Center, the Veteran Affairs Medical Center, and Meharry Medical Center. Individual demographic characteristics were assessed via questionnaire at baseline. Participants underwent a LDCT scan, spirometry, sputum cytology, and research bronchoscopy at the time of enrollment. Participants will be followed yearly for five years. Positive LDCT scans are followed-up according to standard of care. The clinical, imaging and biospecimen data are collected prospectively and stored in a biorepository. Participants are offered smoking cessation counseling at each study visit. RESULTS: A total of 480 participants were enrolled at study baseline and consented to sharing of their data and biospecimens for research. Participants are followed with yearly clinic visits to collect imaging data and biospecimens. To date, a total of 19 cancers (13 adenocarcinomas, 4 squamous cell carcinoma, 1 large cell neuroendocrine and 1 small cell lung cancer) have been identified. CONCLUSION: We established a unique prospective cohort of individuals at high-risk for lung cancer, enrolled at three institutions for which full clinical data, well-annotated LDCT and biospecimens are being collected longitudinally. This repository will allow for the derivation of independent validation of clinical, imaging and molecular biomarkers of risk or diagnosis of lung cancer. Clinical trial registered with ClinicalTrials.gov (NCT01475500).

2.
Cancer Res ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472890

RESUMO

Lung cancer is the leading cause of cancer death globally. An improved risk stratification strategy can increase efficiency of low-dose computed tomography (LDCT) screening. Here we assessed whether individual's genetic background has clinical utility for risk stratification in the context of LDCT screening. Based on 13,119 lung cancer patients and 10,008 controls with European ancestry in the International Lung Cancer Consortium, we constructed a polygenic risk score (PRS) via 10-fold cross-validation with regularized penalized regression. The performance of risk model integrating PRS, including calibration and ability to discriminate, was assessed using UK biobank data (N=335,931). Absolute risk was estimated based on age-specific lung cancer incidence and all-cause mortality as competing risk. To evaluate its potential clinical utility, the PRS distribution was simulated in the National Lung Screening Trial, N=50,772 participants). The lung cancer odds ratio (ORs) for individuals at the top decile of the PRS distribution versus those at bottom 10% was 2.39 (95%CI=1.92-3.00, P=1.80x10-14) in the validation set (trend p-value of 5.26 x 10-20). The OR per standard deviation of PRS increase was 1.26 (95%CI=1.20-1.32, P=9.69x10-23) for overall lung cancer risk in the validation set. When considering absolute risks, individuals at different PRS deciles showed differential trajectories of 5-year and cumulative absolute risk. The age reaching the LDCT screening recommendation threshold can vary by 4 to 8 years, depending on the individual's genetic background, smoking status and family history. Collectively, these results suggest that Individual's genetic background may inform the optimal lung cancer LDCT screening strategy.

3.
Cancer Discov ; 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33318034

RESUMO

Small cell lung cancer (SCLC) is an aggressive disease with dismal survival rates and limited therapeutic options. SCLC development is strongly associated with exposure to tobacco carcinogens. However, additional genetic and environmental risk factors that contribute to SCLC pathogenesis are beginning to emerge. Here, we specifically assess disparities pertaining to SCLC in Black populations. In contrast to non-small cell lung cancer, preliminary data suggest that Black individuals may actually be at a lower risk of developing SCLC relative to white individuals. This difference remains unexplained but urgently needs to be verified in larger data sets, because it could provide important new insights and approaches to understanding this recalcitrant tumor. Importantly, little biological information exists on SCLC in Black individuals, and few patient-derived preclinical SCLC models from diverse ancestries are available in the laboratory. Unfortunately, we note strikingly low numbers of Black participants in clinical trials testing new treatments for SCLC. Evidence further indicates that care for patients with SCLC may vary between communities with a large fraction of Black patients and those without. Together, these observations underscore the need to better investigate genetic, environmental, and socioeconomic factors associated with SCLC development, preclinical research, clinical care, and outcomes.

4.
Genomics ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33161089

RESUMO

Public genomic repositories are notoriously lacking in racially and ethnically diverse samples. This limits the reaches of exploration and has in fact been one of the driving factors for the initiation of the All of Us project. Our particular focus here is to provide a model-based framework for accurately predicting DNA methylation from genetic data using racially sparse public repository data. Epigenetic alterations are of great interest in cancer research but public repository data is limited in the information it provides. However, genetic data is more plentiful. Our phenotype of interest is cervical cancer in The Cancer Genome Atlas (TCGA) repository. Being able to generate such predictions would nicely complement other work that has generated gene-level predictions of gene expression for normal samples. We develop a new prediction approach which uses shared random effects from a nested error mixed effects regression model. The sharing of random effects allows borrowing of strength across racial groups greatly improving predictive accuracy. Additionally, we show how to further borrow strength by combining data from different cancers in TCGA even though the focus of our predictions is DNA methylation in cervical cancer. We compare our methodology against other popular approaches including the elastic net shrinkage estimator and random forest prediction. Results are very encouraging with the shared classified random effects approach uniformly producing more accurate predictions - overall and for each racial group.

5.
Am J Respir Crit Care Med ; 202(7): e95-e112, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000953

RESUMO

Background: There are well-documented disparities in lung cancer outcomes across populations. Lung cancer screening (LCS) has the potential to reduce lung cancer mortality, but for this benefit to be realized by all high-risk groups, there must be careful attention to ensuring equitable access to this lifesaving preventive health measure.Objectives: To outline current knowledge on disparities in eligibility criteria for, access to, and implementation of LCS, and to develop an official American Thoracic Society statement to propose strategies to optimize current screening guidelines and resource allocation for equitable LCS implementation and dissemination.Methods: A multidisciplinary panel with expertise in LCS, implementation science, primary care, pulmonology, health behavior, smoking cessation, epidemiology, and disparities research was convened. Participants reviewed available literature on historical disparities in cancer screening and emerging evidence of disparities in LCS.Results: Existing LCS guidelines do not consider racial, ethnic, socioeconomic, and sex-based differences in smoking behaviors or lung cancer risk. Multiple barriers, including access to screening and cost, further contribute to the inequities in implementation and dissemination of LCS.Conclusions: This statement identifies the impact of LCS eligibility criteria on vulnerable populations who are at increased risk of lung cancer but do not meet eligibility criteria for screening, as well as multiple barriers that contribute to disparities in LCS implementation. Strategies to improve the selection and dissemination of LCS in vulnerable groups are described.


Assuntos
Tomada de Decisão Compartilhada , Detecção Precoce de Câncer/estatística & dados numéricos , Acesso aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Neoplasias Pulmonares/diagnóstico , Fumar/etnologia , Definição da Elegibilidade , Grupos Étnicos/estatística & dados numéricos , Custos de Cuidados de Saúde , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Ciência da Implementação , Cobertura do Seguro , Marketing de Serviços de Saúde/métodos , Medicaid , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Grupos Minoritários/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Encaminhamento e Consulta/estatística & dados numéricos , Fatores Sexuais , Fumar/epidemiologia , Fumar/terapia , Abandono do Hábito de Fumar/estatística & dados numéricos , Classe Social , Estados Unidos
6.
Genet Epidemiol ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32924180

RESUMO

Clinical trial results have recently demonstrated that inhibiting inflammation by targeting the interleukin-1ß pathway can offer a significant reduction in lung cancer incidence and mortality, highlighting a pressing and unmet need to understand the benefits of inflammation-focused lung cancer therapies at the genetic level. While numerous genome-wide association studies (GWAS) have explored the genetic etiology of lung cancer, there remains a large gap between the type of information that may be gleaned from an association study and the depth of understanding necessary to explain and drive translational findings. Thus, in this study we jointly model and integrate extensive multiomics data sources, utilizing a total of 40 genome-wide functional annotations that augment previously published results from the International Lung Cancer Consortium (ILCCO) GWAS, to prioritize and characterize single nucleotide polymorphisms (SNPs) that increase risk of squamous cell lung cancer through the inflammatory and immune responses. Our work bridges the gap between correlative analysis and translational follow-up research, refining GWAS association measures in an interpretable and systematic manner. In particular, reanalysis of the ILCCO data highlights the impact of highly associated SNPs from nuclear factor-κB signaling pathway genes as well as major histocompatibility complex mediated variation in immune responses. One consequence of prioritizing likely functional SNPs is the pruning of variants that might be selected for follow-up work by over an order of magnitude, from potentially tens of thousands to hundreds. The strategies we introduce provide informative and interpretable approaches for incorporating extensive genome-wide annotation data in analysis of genetic association studies.

7.
Front Med ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32889700

RESUMO

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

8.
Int J Cancer ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32914876

RESUMO

At the time of cancer diagnosis, body mass index (BMI) is inversely correlated with lung cancer risk, which may reflect reverse causality and confounding due to smoking behavior. We used two-sample univariable and multivariable Mendelian randomization (MR) to estimate causal relationships of BMI and smoking behaviors on lung cancer and histological subtypes based on an aggregated genome-wide association studies (GWASs) analysis of lung cancer in 29 266 cases and 56 450 controls. We observed a positive causal effect for high BMI on occurrence of small-cell lung cancer (odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.24-2.06, P = 2.70 × 10-4 ). After adjustment of smoking behaviors using multivariable Mendelian randomization (MVMR), a direct causal effect on small cell lung cancer (ORMVMR = 1.28, 95% CI = 1.06-1.55, PMVMR = .011), and an inverse effect on lung adenocarcinoma (ORMVMR = 0.86, 95% CI = 0.77-0.96, PMVMR = .008) were observed. A weak increased risk of lung squamous cell carcinoma was observed for higher BMI in univariable Mendelian randomization (UVMR) analysis (ORUVMR = 1.19, 95% CI = 1.01-1.40, PUVMR = .036), but this effect disappeared after adjustment of smoking (ORMVMR = 1.02, 95% CI = 0.90-1.16, PMVMR = .746). These results highlight the histology-specific impact of BMI on lung carcinogenesis and imply mediator role of smoking behaviors in the association between BMI and lung cancer.

9.
Eur Urol ; 78(3): 316-320, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32409115

RESUMO

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.

10.
Nat Commun ; 11(1): 2220, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393777

RESUMO

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10-15) and replication (adjusted OR = 2.93, P = 2.22 × 10-3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10-22) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk.


Assuntos
Adenocarcinoma/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Neoplasias Pulmonares/genética , Idoso , Alelos , Bases de Dados Genéticas , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Técnicas de Genotipagem , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Judeus/genética , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Razão de Chances , Análise de Sequência com Séries de Oligonucleotídeos , Linhagem , RNA-Seq , Fatores de Risco
11.
Cancer Epidemiol Biomarkers Prev ; 29(7): 1423-1429, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32277007

RESUMO

BACKGROUND: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated. METHODS: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data from The Cancer Genome Atlas (TCGA) project. RESULTS: We identified seven independent SNPs in five lung CDGs that were consistently associated with lung cancer risk in discovery (P < 0.001) and validation (P < 0.05) stages. Among these loci, rs78062588 in TPM3 (1q21.3) was a new lung cancer susceptibility locus (OR = 0.86, P = 1.65 × 10-6). Subgroup analysis by histologic types further identified nine lung CDGs. Analysis of somatic alterations found that in lung adenocarcinomas, rs78062588[C] allele (TPM3 in 1q21.3) was associated with elevated somatic copy number of TPM3 (OR = 1.16, P = 0.02). In lung adenocarcinomas, rs1611182 (HLA-A in 6p22.1) was associated with truncation mutations of the transcriptional misregulation in cancer pathway (OR = 0.66, P = 1.76 × 10-3). CONCLUSIONS: Genetic variants can regulate functions of lung CDGs and influence lung cancer susceptibility. IMPACT: Our findings might help unravel biological mechanisms underlying lung cancer susceptibility.

12.
Ann Am Thorac Soc ; 17(4): 399-405, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017612

RESUMO

Lung cancer is the leading cause of cancer mortality in the United States. Certain groups are at increased risk of developing lung cancer and experience greater morbidity and mortality than the general population. Lung cancer screening provides an opportunity to detect lung cancer at an early stage when surgical intervention can be curative; however, current screening guidelines may overlook vulnerable populations with disproportionate lung cancer burden. This review aims to characterize disparities in lung cancer screening eligibility, as well as access to lung cancer screening, focusing on underrepresented racial/ethnic minorities and high-risk populations, such as individuals with human immunodeficiency virus. We also explore potential system- and patient-level barriers that may influence smoking patterns and healthcare access. Improving access to high-quality health care with a focus on smoking cessation is essential to reduce the burden of lung cancer experienced by vulnerable populations.

13.
Nat Commun ; 11(1): 27, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911640

RESUMO

Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV1: rg = 0.098, p = 2.3 × 10-8) and the ratio of FEV1 to forced vital capacity (FEV1/FVC: rg = 0.137, p = 2.0 × 10-12). Mendelian randomization analyses demonstrate that reduced FEV1 increases squamous cell carcinoma risk (odds ratio (OR) = 1.51, 95% confidence intervals: 1.21-1.88), while reduced FEV1/FVC increases the risk of adenocarcinoma (OR = 1.17, 1.01-1.35) and lung cancer in never smokers (OR = 1.56, 1.05-2.30). These findings support a causal role of pulmonary impairment in lung cancer etiology. Integrative analyses reveal that pulmonary function instruments, including 73 novel variants, influence lung tissue gene expression and implicate immune-related pathways in mediating the observed effects on lung carcinogenesis.


Assuntos
Neoplasias Pulmonares/genética , Pulmão/fisiopatologia , Adulto , Idoso , Feminino , Volume Expiratório Forçado , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Testes de Função Respiratória , Capacidade Vital
14.
Int J Cancer ; 146(10): 2855-2864, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31577861

RESUMO

Genome-wide association studies (GWAS) have identified 45 susceptibility loci associated with lung cancer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant genetic polymorphisms in the human genome. INDELs are highly associated with multiple human diseases, including lung cancer. However, limited studies with large-scale samples have been available to systematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large-scale meta-analysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional annotations were performed to further explore the potential function of lung cancer risk INDELs. Conditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci were identified in genome-wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 × 10-8 ; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 × 10-7 ; 12p13.31: rs71450133, Deletion, OR = 1.09, p = 8.83 × 10-7 ; and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 × 10-8 ). The eQTL analysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by regulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, the INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be potentially functional genetic variants for lung cancer risk. Further functional experiments are needed to better understand INDEL mechanisms in carcinogenesis.


Assuntos
Predisposição Genética para Doença/genética , Mutação INDEL/genética , Neoplasias Pulmonares/genética , Estudo de Associação Genômica Ampla , Humanos
15.
Int J Cancer ; 146(7): 1862-1878, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31696517

RESUMO

We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large-scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome-wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never- and ever-smokers). We performed replication analysis using lung data from the Genotype-Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever-smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E-99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E-6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3-adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E-5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk.


Assuntos
Biomarcadores Tumorais , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Pulmonares/genética , Transcriptoma , Linhagem Celular Tumoral , Humanos , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
18.
JAMA Oncol ; 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31246249

RESUMO

Importance: The United States Preventive Services Task Force (USPSTF) recommends low-dose computed tomography screening for lung cancer. However, USPSTF screening guidelines were derived from a study population including only 4% African American smokers, and racial differences in smoking patterns were not considered. Objective: To evaluate the diagnostic accuracy of USPSTF lung cancer screening eligibility criteria in a predominantly African American and low-income cohort. Design, Setting, and Participants: The Southern Community Cohort Study prospectively enrolled adults visiting community health centers across 12 southern US states from March 25, 2002, through September 24, 2009, and followed up for cancer incidence through December 31, 2014. Participants included African American and white current and former smokers aged 40 through 79 years. Statistical analysis was performed from May 11, 2016, to December 6, 2018. Exposures: Self-reported race, age, and smoking history. Cumulative exposure smoking histories encompassed most recent follow-up questionnaires. Main Outcomes and Measures: Incident lung cancer cases assessed for eligibility for lung cancer screening using USPSTF criteria. Results: Among 48 364 ever smokers, 32 463 (67%) were African American and 15 901 (33%) were white, with 1269 incident lung cancers identified. Among all 48 364 Southern Community Cohort Study participants, 5654 of 32 463 African American smokers (17%) were eligible for USPSTF screening compared with 4992 of 15 901 white smokers (31%) (P < .001). Among persons diagnosed with lung cancer, a significantly lower percentage of African American smokers (255 of 791; 32%) was eligible for screening compared with white smokers (270 of 478; 56%) (P < .001). The lower percentage of eligible lung cancer cases in African American smokers was primarily associated with fewer smoking pack-years among African American vs white smokers (median pack-years: 25.8 [interquartile range, 16.9-42.0] vs 48.0 [interquartile range, 30.2-70.5]; P < .001). Racial disparity was observed in the sensitivity and specificity of USPSTF guidelines between African American and white smokers for all ages. Lowering the smoking pack-year eligibility criteria to a minimum 20-pack-year history was associated with an increased percentage of screening eligibility of African American smokers and with equitable performance of sensitivity and specificity compared with white smokers across all ages (for a 55-year-old current African American smoker, sensitivity increased from 32.2% to 49.0% vs 56.5% for a 55-year-old white current smoker; specificity decreased from 83.0% to 71.6% vs 69.4%; P < .001). Conclusions and Relevance: Current USPSTF lung cancer screening guidelines may be too conservative for African American smokers. The findings suggest that race-specific adjustment of pack-year criteria in lung cancer screening guidelines would result in more equitable screening for African American smokers at high risk for lung cancer.

19.
Ann Epidemiol ; 35: 1-3, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31036443

RESUMO

The under-representation of women in leadership in scientific fields presents a serious problem. Gender diversity is integral to innovation and productivity, and inequality leads to loss of gender talent in science including epidemiology. This policy brief summarizes some of the key dimensions and determinants contributing to gender-equity gaps in epidemiology and other scientific fields, relevant to developed countries where there is more published evidence. Women in scientific fields hold fewer positions on editorial boards, lack equal representation in speaking engagements at conferences, and are less likely to publish or receive top tier grant funding. Reasons for these inequities range from unconscious bias, biased promotion systems, and traditional norms in the division of family life and labor in our society leading to the attrition of women in academia. Addressing the problem of gender inequity, as a component of gender inequality, will provide an ethical basis to advance innovation. Data on gender equity in the field of epidemiology are sparse. We call on academic institutions, professional societies and associations, and editorial boards relevant to epidemiology (as well as other academic disciplines more broadly) to take meaningful action to build an evidence base as to the extent of gender inequities in epidemiologic research, teaching, policy, and practice. We outline some of the necessary steps required to achieve gender equity, such as career development and mentoring programs, institutional support, and programs to address bias.


Assuntos
Mobilidade Ocupacional , Liderança , Epidemiologia , Feminino , Humanos , Mentores , Salários e Benefícios , Sexismo
20.
Am J Phys Anthropol ; 169(3): 482-497, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31125126

RESUMO

OBJECTIVES: From a genetic perspective, relatively little is known about how mass emigrations of African, European, and Asian peoples beginning in the 16th century affected Indigenous Caribbean populations. Therefore, we explored the impact of serial colonization on the genetic variation of the first Caribbean islanders. MATERIALS AND METHODS: Sixty-four members of St. Vincent's Garifuna Community and 36 members of Trinidad's Santa Rosa First People's Community (FPC) of Arima were characterized for mitochondrial DNA and Y-chromosome diversity via direct sequencing and targeted SNP and STR genotyping. A subset of 32 Garifuna and 18 FPC participants were genotyped using the GenoChip 2.0 microarray. The resulting data were used to examine genetic diversity, admixture, and sex biased gene flow in the study communities. RESULTS: The Garifuna were most genetically comparable to African descendant populations, whereas the FPC were more similar to admixed American groups. Both communities also exhibited moderate frequencies of Indigenous American matrilines and patrilines. Autosomal SNP analysis indicated modest Indigenous American ancestry in these populations, while both showed varying degrees of African, European, South Asian, and East Asian ancestry, with patterns of sex-biased gene flow differing between the island communities. DISCUSSION: These patterns of genetic variation are consistent with historical records of migration, forced, or voluntary, and suggest that different migration events shaped the genetic make-up of each island community. This genomic study is the highest resolution analysis yet conducted with these communities, and provides a fuller understanding of the complex bio-histories of Indigenous Caribbean peoples in the Lesser Antilles.


Assuntos
Grupos de Populações Continentais/genética , Grupos de Populações Continentais/história , Adulto , Cromossomos Humanos Y/genética , DNA/genética , DNA Mitocondrial/genética , Feminino , Genética Populacional , História do Século XV , História do Século XVI , História do Século XVIII , História do Século XIX , História Antiga , Migração Humana/história , Humanos , Masculino , São Vicente e Granadinas , Trinidad e Tobago
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