Global Epidemiology of Lung Cancer.

While lung cancer has been the leading cause of cancer-related deaths for many years in the United States, incidence and mortality statistics - among other measures - vary widely worldwide. The aim of this study was to review the evidence on lung cancer epidemiology, including data of international scope with comparisons of economically, socially, and biologically different patient groups. In industrialized nations, evolving social and cultural smoking patterns have led to rising or plateauing rates of lung cancer in women, lagging the long-declining smoking and cancer incidence rates in men. In contrast, emerging economies vary widely in smoking practices and cancer incidence but commonly also harbor risks from environmental exposures, particularly widespread air pollution. Recent research has also revealed clinical, radiologic, and pathologic correlates, leading to greater knowledge in molecular profiling and targeted therapeutics, as well as an emphasis on the rising incidence of adenocarcinoma histology. Furthermore, emergent evidence about the benefits of lung cancer screening has led to efforts to identify high-risk smokers and development of prediction tools. This review also includes a discussion on the epidemiologic characteristics of special groups including women and nonsmokers. Varying trends in smoking largely dictate international patterns in lung cancer incidence and mortality. With declining smoking rates in developed countries and knowledge gains made through molecular profiling of tumors, the emergence of new risk factors and disease features will lead to changes in the landscape of lung cancer epidemiology

Racial disparities in occupational risks and lung cancer incidence: Analysis of the National Lung Screening Trial.

The relationship between racial disparities in occupational risk and lung cancer diagnosis is not well defined. We examined occupational exposure to asbestos, silica, and other workplace chemicals, fumes, or dusts as reported in the National Lung Screening Trial (NLST). Descriptive analyses and multivariate logistic regression models were performed. Among the NLST study cohort, 3.9% were diagnosed with lung cancer. African-Americans had a higher rate of lung cancer diagnosis than White individuals (4.3% vs. 3.9%). About 28% reported at least one occupational exposure, including 6.5% exposed to silica and 4.7% to asbestos. African-Americans reported occupational exposure more frequently than White participants, including exposures to asbestos and silica. In a multivariate model, the interactions of all measures of occupational exposures and smoking status were significant. Current smokers with occupational exposures had higher odds of lung cancer diagnosis (aOR = 2.01, 95% CI = 1.76-2.30 for any exposure as well as higher odds after silica (aOR = 2.35, 95% CI = 1.89-2.91) or asbestos (aOR = 1.97, 95% CI = 1.52-2.56) exposure compared to former smokers without any exposures. African-Americans had higher odds of lung cancer diagnosis than White individuals (aOR = 1.24 to 1.25, 95% CI = 1.01-1.54). Our findings indicate that we need more effective public health prevention programs, especially for minorities who may have disproportionately greater occupational exposures due to socioeconomic constructs and barriers. Interventions may include education about occupational risks and lung cancer screening or instituting workplace policies for smoke-free environments with tobacco cessation support

Black patients referred to a lung cancer screening program experience lower rates of screening and longer time to follow-up.

BACKGROUND: Racial disparities are well-documented in preventive cancer care, but they have not been fully explored in the context of lung cancer screening. We sought to explore racial differences in lung cancer screening outcomes within a lung cancer screening program (LCSP) at our urban academic medical center including differences in baseline low-dose computed tomography (LDCT) results, time to follow-up, adherence, as well as return to annual screening after additional imaging, loss to follow-up, and cancer diagnoses in patients with positive baseline scans. METHODS: A historical cohort study of patients referred to our LCSP was conducted to extract demographic and clinical characteristics, smoking history, and lung cancer screening outcomes. RESULTS: After referral to the LCSP, blacks had significantly lower odds of receiving LDCT compared to whites, even while controlling for individual lung cancer risk factors and neighborhood-level factors. Blacks also demonstrated a trend toward delayed follow-up, decreased adherence, and loss to follow-up across all Lung-RADS categories. CONCLUSIONS: Overall, lung cancer screening annual adherence rates were low, regardless of race, highlighting the need for increased patient education and outreach. Furthermore, the disparities in race we identified encourage further research with the purpose of creating culturally competent and inclusive LCSPs

Interrogating Genes That Mediate Chlamydia trachomatis Survival in Cell Culture Using Conditional Mutants and Recombination

Intracellular bacterial pathogens in the family Chlamydiaceae are causes of human blindness, sexually transmitted disease, and pneumonia. Genetic dissection of the mechanisms of chlamydial pathogenicity has been hindered by multiple limitations, including the inability to inactivate genes that would prevent the production of elementary bodies. Many genes are also Chlamydia-specific genes, and chlamydial genomes have undergone extensive reductive evolution, so functions often cannot be inferred from homologs in other organisms. Conditional mutants have been used to study essential genes of many microorganisms, so we screened a library of 4,184 ethyl methanesulfonate-mutagenized Chlamydia trachomatis isolates for temperature-sensitive (TS) mutants that developed normally at physiological temperature (37°C) but not at nonphysiological temperatures. Heat-sensitive TS mutants were identified at a high frequency, while cold-sensitive mutants were less common. Twelve TS mutants were mapped using a novel markerless recombination approach, PCR, and genome sequencing. TS alleles of genes that play essential roles in other bacteria and chlamydia-specific open reading frames (ORFs) of unknown function were identified. Temperature-shift assays determined that phenotypes of the mutants manifested at distinct points in the developmental cycle. Genome sequencing of a larger population of TS mutants also revealed that the screen had not reached saturation. In summary, we describe the first approach for studying essential chlamydial genes and broadly applicable strategies for genetic mapping in Chlamydia spp. and mutants that both define checkpoints and provide insights into the biology of the chlamydial developmental cycle. IMPORTANCE: Study of the pathogenesis of Chlamydia spp. has historically been hampered by a lack of genetic tools. Although there has been recent progress in chlamydial genetics, the existing approaches have limitations for the study of the genes that mediate growth of these organisms in cell culture. We used a genetic screen to identify conditional Chlamydia mutants and then mapped these alleles using a broadly applicable recombination strategy. Phenotypes of the mutants provide fundamental insights into unexplored areas of chlamydial pathogenesis and intracellular biology. Finally, the reagents and approaches we describe are powerful resources for the investigation of these organisms

The Philadelphia Lung Cancer Learning Community: A Multi-Health-System, Citywide Approach to Lung Cancer Screening

Background Lung cancer screening uptake for individuals at high risk is generally low across the United States, and reporting of lung cancer screening practices and outcomes is often limited to single hospitals or institutions. We describe a citywide, multicenter analysis of individuals receiving lung cancer screening integrated with geospatial analyses of neighborhood-level lung cancer risk factors. Methods The Philadelphia Lung Cancer Learning Community consists of lung cancer screening clinicians and researchers at the 3 largest health systems in the city. This multidisciplinary, multi-institutional team identified a Philadelphia Lung Cancer Learning Community study cohort that included 11 222 Philadelphia residents who underwent low-dose computed tomography for lung cancer screening from 2014 to 2021 at a Philadelphia Lung Cancer Learning Community health-care system. Individual-level demographic and clinical data were obtained, and lung cancer screening participants were geocoded to their Philadelphia census tract of residence. Neighborhood characteristics were integrated with lung cancer screening counts to generate bivariate choropleth maps. Results The combined sample included 37.8% Black adults, 52.4% women, and 56.3% adults who currently smoke. Of 376 residential census tracts in Philadelphia, 358 (95.2%) included 5 or more individuals undergoing lung cancer screening, and the highest counts were geographically clustered around each health system’s screening sites. A relatively low percentage of screened adults resided in census tracts with high tobacco retailer density or high smoking prevalence. Conclusions The sociodemographic characteristics of lung cancer screening participants in Philadelphia varied by health system and neighborhood. These results suggest that a multicenter approach to lung cancer screening can identify vulnerable areas for future tailored approaches to improving lung cancer screening uptake. Future directions should use these findings to develop and test collaborative strategies to increase lung cancer screening at the community and regional levels

Synaptic processes and immune-related pathways implicated in Tourette syndrome

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Analysis of Lung Cancer Screening by Race After USPSTF Expansion of Screening Eligibility in 2021.

This cross-sectional study examines differences among individuals deemed eligible for lung cancer screening under USPSTF 2013 vs under USPTSF 2021 guidelines

Racial difference in BMI and lung cancer diagnosis: analysis of the National Lung Screening Trial

Abstract Background The inverse relationship between BMI and lung cancer diagnosis is well defined. However, few studies have examined the racial differences in these relationships. The purpose of this paper is to explore the relationships amongst race, BMI, and lung cancer diagnosis using the National Lung Screening Trial (NLST) data. Methods Multivariate regression analysis was used to analyze the BMI, race, and lung cancer diagnosis relationships. Results Among 53,452 participants in the NLST cohort, 3.9% were diagnosed with lung cancer, 43% were overweight, and 28% were obese. BMI was inversely related to lung cancer diagnosis among Whites: those overweight (aOR = .83, 95%CI = .75-.93), obese (aOR = .64, 95%CI = .56-.73) were less likely to develop lung cancer, compared to those with normal weight. These relationships were not found among African-Americans. Conclusion Our findings indicate that the inverse relationship of BMI and lung cancer risk among Whites is consistent, whereas this relationship is not significant for African-Americans. In consideration of higher lung cancer incidence among African Americans, we need to explore other unknown mechanisms explaining this racial difference