Increased Risk Of Lung Cancer Research Articles

The fate of an inhaled cigarette puff in the human respiratory tract

Objective Cigarette smoking can lead to a host of adverse health effects such as lung and heart disease. Increased lung cancer risk is associated with inhalation of carcinogens present in a puff of smoke. These carcinogenic compounds deposit in the lung at different sites and trigger a cascade of events leading to adverse outcomes. Understanding the site-specific deposition of various smoke constituents will inform the study of respiratory diseases from cigarette smoking. We previously developed a deposition model for inhalation of aerosol from electronic nicotine delivery systems. In this study, the model was modified to simulate inhalation of cigarette smoke consisting of soluble and insoluble tar, nicotine, and cigarette-specific constituents that are known or possible human carcinogens. Materials and Methods The deposition model was further modified to account for nicotine protonation and other cigarette-specific physics-based mechanisms that affect smoke deposition. Model predictions showed a total respiratory tract uptake in the lung for formaldehyde (99%), nicotine (80%), and benzo[a]pyrene (60%). Results The site of deposition and uptake depended primarily on the constituent’s saturation vapor pressure. High vapor pressure constituents such as formaldehyde were preferentially absorbed in the oral cavity and proximal lung regions, while low vapor pressure constituents such as benzo[a]pyrene were deposited in the deep lung regions. Model predictions of exhaled droplet size, droplet retention, nicotine retention, and uptake of aldehydes compared favorably with experimental data. Conclusion The deposition model can be integrated into exposure assessments and other studies that evaluate potential adverse health effects from cigarette smoking.

Associations of prior lung diseases on risk of lung cancer in populations with no smoking history: A systematic review and meta-analysis.

10561 Background: Individuals without prior tobacco use account for a growing proportion of lung cancer cases, but the impact of prior lung diseases on lung cancer risk in this population remains unclear. We performed a meta-analysis of studies examining the association of prior lung diseases – tuberculosis (TB), asthma (AS), and chronic bronchitis (CB) – with lung cancer risk among individuals without prior tobacco use. Methods: PubMed and Embase were searched from inception to Jan 20th, 2024 for studies examining the association between TB, AS, and/or CB and lung cancer risk in populations over 18 years old who never smoke. Studies were excluded if (1) “never-smoking” was not defined as having never smoked or smoked less than 100 cigarettes in their lifetime; (2) they were not written in English, Mandarin, or Korean; (2) odds ratios (OR)/hazard ratios (HR) were not reported. Summary effect estimates with 95% CI were calculated for case-control (summary OR) and cohort (summary HR) studies using random effects models with inverse variance weighting. Subgroup meta-analyses and meta-regressions were conducted among case-control studies by continent [Asia vs. non-Asia (North America and Europe)]. There was insufficient information to examine differences across the subgroups of sex and race and ethnicity. Results: 17 case-control studies and five cohort studies were examined. Among case-control studies, history of TB (13 studies), AS (10 studies), and CB (nine studies) were statistically significantly associated with an increased risk of lung cancer in patients without prior tobacco use (TB: summary OR=1.75, 95% CI 1.43-2.15, I2 = 29; AS: summary OR=1.46, 95% CI 1.06-2.02, I2 = 34; CB: summary OR=1.36, 95% CI 1.07-1.72, I2 = 0). Among cohort studies, TB (four studies) was associated with a statistically significant increase in lung cancer risk (summary HR=1.81, 95% CI 1.34-2.44, I2 = 44). There were insufficient number of cohort studies to summarize the associations of CB (no studies) or AS (one study) with lung cancer risk. The summary OR for TB and AS with lung cancer risk was larger in Asian vs. non-Asian populations (TB: Asian populations summary OR=1.79 95% CI 1.40-2.28, I2 = 47 vs. non-Asian populations summary OR=1.47 95% CI 0.88-2.44, I2 = 0; AS: Asian populations summary OR=2.63 95% CI 1.10-6.28, I2 = 40 vs. non-Asian populations summary OR=1.31 95% CI 0.96-1.79, I2 = 20). However, there was no evidence of heterogeneity in summary OR by continent using meta-regression (TB: p=0.58; AS: p=0.16). Conclusions: In this meta-analysis, history of TB, AS, and CB were associated with lung cancer risk among populations who never smoked, informing potential etiologies of the shifting global burden of lung cancer. Future studies examining these associations should analyze more diverse patient populations and disaggregate findings by sex, race and ethnicity, socioeconomic status, and geography.

Protein Programmed Death-Ligand 1 Expression in Non-Small Cell Lung Cancer (NSCLC) and Its Correlation to Smoking Status in North Sumatera Population

Tobacco smoking is associated to the increase risk of lung cancer, and smoking could also trigger the tumour proportion score from programmed death ligand (PD-L1). This study aims to identify the correlation of non-small cell lung cancer (NSCLC) with the PD-L1 expression and smoking profile on the North Sumatra Population. Lung cancer is a significant health issue worldwide, where it is the leading cause of death in men. In Indonesia, lung cancer ranks second in terms of incidence overall and first in men. The 5-year prevalence of lung cancer in Indonesia is 10.85 per 100,000 population. The case fatality rate (CFR) for lung cancer in Indonesia is 86.91%. This research implemented a descriptive study with cross-sectional design. 100 of patients with lung cancer were recruited, however; only 52 patients were diagnosed with NSCLC based on histopathological results. Subsequently, 35 samples were included in accordance to inclusion criteria. Staining on Ventana 22C3 platform was performed in Dharmais Cancer Hospital, and tumour proportion score was assessed by two experts of Pathologist. This study was carried out from August 2019 to September 2020. Results: Characteristics of patients with NSCLC to the PD-L1 expression were found more in male patients with percentage of 88.6%, whereas the most common type of cancer is adenocarcinoma, accounting for 97.14% of cases with mild degree smoking index for 45.7% (Brinkman index) and IV-stage of clinical status for 68.6%. The tumour proportion score with 1-49% was 51.4% with high expression of PD-L1 (positive) for 74.28%, while lower expression of PD-L1 accounted for 45%. There is a correlation between PD-L1 expression and smoking status in NSCLC patients, with p-value of 0.037 (<0.05).

Association of Lung Cancer Risk With the Presence of Both Lung Nodules and Emphysema in a Lung Cancer Screening Trial.

The coexistence of emphysema and lung nodules could interact with each other and then lead to potential higher lung cancer risk. The study aimed to explore the association between emphysema combined with lung nodules and lung cancer risk. A total of 21,949 participants from the National Lung Screening Trial (NLST) who underwent low-dose computed tomography (LDCT) examination were included. Participants were categorized into four groups (NENN group (non-emphysema and non-nodules), E group (emphysema without nodules), N group (nodules without emphysema), and E + N group (nodules with emphysema)) according to whether there were lung nodules and emphysema. Multivariable Cox regression and stratified analyses were performed to estimate the association between the four groups and lung cancer risk. Among the 21,949 participants, there were 9,040 (41.2%), 5,819 (26.5%), 4,737 (21.6%), and 2,353 (10.7%) participants in the NENN group, E group, N group, and E + N group. The risk of lung cancer incidence increased in turn in NENN group, E group, N group and E + N group. Compared with NENN group, the age-adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) of lung cancer incidence were 2.07 (1.69 - 2.54) for E group, 4.13 (3.47 - 5.05) for N group, and 6.26 (5.14 - 7.62) for E + N group. The association was robust to adjustment for potential confounders (1.83 (1.47 - 2.27) for E group, 3.97 (3.24 - 4.86) for N group, and 5.23 (4.28 - 6.48) for E + N group). Comparable results as the lung cancer incidence were observed for lung cancer mortality, whether in age-adjusted model (E group: 1.85 (1.39 - 2.46), N group: 2.49 (1.89 - 3.29), E + N group: 4.27 (3.21 - 5.68)) or fully adjusted model (E group: 1.56 (1.15 - 2.11), N group: 2.43 (1.81 - 3.26), E + N group: 3.39 (2.50 - 4.61)). However, the trend of all-cause mortality risk among the four groups was somewhat different from that of lung cancer risk, whether in age-adjusted model (1.37 (1.21 - 1.54) for E group, 1.06 (0.92 - 1.21) for N group, and 1.75 (1.51 - 2.02) for E + N group) or fully adjusted model (1.26 (1.10 - 1.44) for E group, 1.09 (0.94 - 1.27) for N group, and 1.52 (1.30 - 1.79) for E + N group). Based on a large-scale lung cancer screening trial in the United States, this study demonstrated that either emphysema or lung nodules can increase lung cancer risk, and lung nodules combined with emphysema can further increase the lung cancer risk and all-cause mortality. The significance of these findings for lung cancer screening should be evaluated.

Association of decreased estimated glomerular filtration rate with lung cancer risk in the Korean population.

Inconsistent results are available regarding the association between low estimated glomerular filtration rate (eGFR) and lung cancer risk. We aimed to explore the risk of lung cancer according to eGFR category in the Korean population. We included 358,293 adults who underwent health checkups between 2009 and 2010, utilizing data from the National Health Insurance Service-National Sample Cohort. Participants were categorized into 3 groups based on their baseline eGFR, as determined using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR ≥90 mL/min/1.73 m2), group 2 (eGFR ≥60 to <90 mL/min/1.73 m2), and group 3 (eGFR <60 mL/min/1.73 m2). Incidences of lung cancer were identified using the corresponding codes from the International Classification of Diseases, 10th revision. Multivariate Cox proportional hazard models were employed to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence up to 2019. In multivariate analysis, group 2 exhibited a 26% higher risk of developing lung cancer than group 1 (HR, 1.26; 95% CI, 1.19 to 1.35). Furthermore, group 3 demonstrated a 72% elevated risk of lung cancer relative to group 1 (HR, 1.72; 95% CI, 1.58 to 1.89). Among participants with dipstick proteinuria of 2+ or greater, group 3 faced a significantly higher risk of lung cancer than group 1 (HR, 2.93; 95% CI, 1.37 to 6.24). Low eGFR was significantly associated with increased lung cancer risk within the Korean population. A particularly robust association was observed in individuals with severe proteinuria, emphasizing the need for further investigation.

Myriad Presentation of Adenocarcinoma Lung

Lung adenocarcinoma is the leading cause of cancer related deaths worldwide. The causes for adenocarcinoma include smoking, air pollution, family history, occupational exposure, silica, asbestos, diesel fumes, and heavy metals. Smoking increases lung cancer risk by 5- to 10 fold with a clear dose–response relationship and environmental tobacco smoke among non-smokers increases lung cancer risk by about 20 %.[1] Lung cancers can be classified into two types based on histology as small cell carcinoma and non-small cell carcinoma. Adenocarcinoma falls under non-small cell carcinoma. Non-small cell carcinoma is further classified into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Polyserositis is a condition where there is an inflammation of serous membranes with effusion. Most common sites are pleura and pericardium presenting with symptoms like chest pain, and shortness of breath.[2] The causes include idiopathic, infectious disease like tuberculosis, autoimmune conditions like SLE, and neoplasm. Neoplasm is the most common cause (nearly one-third of cases). Autoimmune disease like Adult-onset Still's disease presents with cardiac and pulmonary involvement pleural effusion, pericarditis and serositis.[3] A possible manifestation of systemic lupus erythematosus is extensive serous involvement like pericardial effusion and pleural effusion.[4] In this case report, we discuss the presentation of adenocarcinoma and pericardial effusion with liver metastasis in a 74-year-old female.

The interaction effects of zinc and polygenic risk score with benzo[a]pyrene exposure on lung cancer risk: A prospective case-cohort study among Chinese populations

The relationship of exposure to benzo[a]pyrene (BaP) with lung cancer risk has been firmly established, but whether this association could be modified by other environmental or genetic factors remains to be explored. To investigate whether and how zinc (Zn) and genetic predisposition modify the association between BaP and lung cancer, we performed a case-cohort study with a 5.4-year median follow-up duration, comprising a representative subcohort of 1399 participants and 359 incident lung cancer cases. The baseline concentrations of benzo[a]pyrene diol epoxide-albumin adduct (BPDE-Alb) and Zn were quantified. We also genotyped the participants and computed the polygenic risk score (PRS) for lung cancer. Our findings indicated that elevated BPDE-Alb and PRS were linked to increased lung cancer risk, with the HR (95%CI) of 1.54 (1.36, 1.74) per SD increment in ln-transformed BPDE-Alb and 1.27 (1.14, 1.41) per SD increment in PRS, but high plasma Zn level was linked to a lower lung cancer risk [HR (95%CI)=0.77 (0.66, 0.91) per SD increment in ln-transformed Zn]. There was evidence of effect modification by Zn on BaP-lung cancer association (P for multiplicative interaction = 0.008). As Zn concentrations increased from the lowest to the highest tertile, the lung cancer risk per SD increment in ln-transformed BPDE-Alb decreased from 2.07 (1.48, 2.89) to 1.33 (0.90, 1.95). Additionally, we observed a significant synergistic interaction of BPDE-Alb and PRS [RERI (95%CI) = 0.85 (0.03, 1.67)], with 42% of the incident lung cancer cases among individuals with high BPDE-Alb and high PRS attributable to their additive effect [AP (95%CI) = 0.42 (0.14, 0.69)]. This study provided the first prospective epidemiological evidence that Zn has protective effect against BaP-induced lung tumorigenesis, whereas high genetic risk can enhance the harmful effect of BaP. These findings may provide novel insight into the environment-environment and environment-gene interaction underlying lung cancer development, which may help to develop prevention and intervention strategies to manage BaP-induced lung cancer.

Lung cancer risk and occupational pulmonary fibrosis: systematic review and meta-analysis.

Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer. Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer? A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model. 52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13-1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67-3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34-1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account. This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present.

Identification of pathogenic germline variants in a large Chinese lung cancer cohort by clinical sequencing.

Genetic factors play significant roles in the tumorigenicity of lung cancer; however, there is lack of systematic and large-scale characterization of pathogenic germline variants for lung cancer. In this study, germline variants in 146 preselected cancer-susceptibility genes were detected in 17 904 Chinese lung cancer patients by clinical next-generation sequencing. Among 17 904 patients, 1738 patients (9.7%) carried 1840 pathogenic/likely pathogenic (P/LP) variants from 87 cancer-susceptibility genes. SBDS (SBDS ribosome maturation factor) (1.37%), TSHR (thyroid stimulating hormone receptor) (1.20%), BLM (BLM RecQ like helicase) (0.62%), BRCA2 (BRCA2 DNA repair associated) (0.62%), and ATM (ATM serine/threonine kinase) (0.45%) were the top five genes with the highest overall prevalence. The top mutated pathways were all involved in DNA damage repair (DDR). Case-control analysis showed SBDS c.184A>T(p.K62*), TSHR c.1574T>C(p.F525S), BRIP1 (BRCA1 interacting helicase 1) c.1018C>T(p.L340F), and MUTYH (mutY DNA glycosylase) c.55C>T(p.R19*) were significantly associated with increased lung cancer risk (q value < 0.05). P/LP variants in certain genes were associated with early onset of lung cancer. Our study indicates that Chinese lung cancer patients have a higher prevalence of P/LP variants than previously reported. P/LP variants are distributed in multiple pathways and dominated by DNA damage repair-associated pathways. The association between identified P/LP variants and lung cancer risk requires further studies for verification.

Lung nodule malignancy classification with associated pulmonary fibrosis using 3D attention-gated convolutional network with CT scans

BackgroundChest Computed tomography (CT) scans detect lung nodules and assess pulmonary fibrosis. While pulmonary fibrosis indicates increased lung cancer risk, current clinical practice characterizes nodule risk of malignancy based on nodule size and smoking history; little consideration is given to the fibrotic microenvironment.PurposeTo evaluate the effect of incorporating fibrotic microenvironment into classifying malignancy of lung nodules in chest CT images using deep learning techniques.Materials and methodsWe developed a visualizable 3D classification model trained with in-house CT dataset for the nodule malignancy classification task. Three slightly-modified datasets were created: (1) nodule alone (microenvironment removed); (2) nodule with surrounding lung microenvironment; and (3) nodule in microenvironment with semantic fibrosis metadata. For each of the models, tenfold cross-validation was performed. Results were evaluated using quantitative measures, such as accuracy, sensitivity, specificity, and area-under-curve (AUC), as well as qualitative assessments, such as attention maps and class activation maps (CAM).ResultsThe classification model trained with nodule alone achieved 75.61% accuracy, 50.00% sensitivity, 88.46% specificity, and 0.78 AUC; the model trained with nodule and microenvironment achieved 79.03% accuracy, 65.46% sensitivity, 85.86% specificity, and 0.84 AUC. The model trained with additional semantic fibrosis metadata achieved 80.84% accuracy, 74.67% sensitivity, 84.95% specificity, and 0.89 AUC. Our visual evaluation of attention maps and CAM suggested that both the nodules and the microenvironment contributed to the task.ConclusionThe nodule malignancy classification performance was found to be improving with microenvironment data. Further improvement was found when incorporating semantic fibrosis information.

Exploring the Disparity in Indoor/Outdoor Time and Radon Exposure as Possible Factors Contributing to the Unexpected Increase in Lung Cancer Risk among Non- Smoking Women

Exploring the Disparity in Indoor/Outdoor Time and Radon Exposure as Possible Factors Contributing to the Unexpected Increase in Lung Cancer Risk among Non- Smoking Women

Impact of IL-6 and IL-1β Gene Variants on Non-small-cell Lung Cancer Risk in Egyptian Patients

AbstractLung cancer is a serious health and life issue, with the fastest-growing incidence and fatality rates worldwide. It is now clear that inflammation is a key factor involved in all aspects of carcinogenesis, notably lung cancer development. Genetic changes, including polymorphisms in inflammatory genes, are supposed to be a significant cause of increased lung cancer risk. The main idea of this research was to disclose the linkage between both IL-6 rs1800795 and IL-1β rs16944 variants and susceptibility to non-small-cell lung cancer (NSCLC) in Egyptians. This case–control design was composed of 127 cases and 138 controls, which were genotyped using the ARMS-PCR technique. To examine the NSCLC susceptibility under various genetic models, the odds ratio (OR) and 95% confidence intervals (CIs) were determined by logistic regression. Rs1800795 of the IL-6 gene was linked to higher odds of NSCLC under the allele model (adjusted, OR 2.28; 95% CI 1.2–4.33; p = 0.011). In the genetic models, IL-6 rs1800795 elevated the odds of NSCLC, while IL-1β rs16944 decreased the odds of NSCLC. Stratification analysis showed that IL-6 rs1800795 greatly increased the NSCLC risk in females and adenocarcinoma subtypes, whereas IL-1β rs16944 largely decreased the NSCLC risk for males, patients aged &lt; 55, and nonsmokers. Regarding clinical data, the IL-6 variant was remarkably correlated with tumor size. This work primarily established that IL-6 and IL-1β variants have a great impact on NSCLC development in the Egyptian population; thus, it may be a supportive guide for earlier NSCLC prevention.

Serum-based biomarkers associated with lung cancer risk and cause-specific mortality in the German randomized Lung Cancer Screening Intervention (LUSI) trial.

Lung cancer (LC) screening can be optimized using individuals' estimated risks of having a detectable lung tumor, as well as of mortality risk by competing causes, to guide decisions on screening eligibility, ideal screening intervals and stopping ages. Besides age, sex and smoking history, blood-based biomarkers may be used to improve the assessment of LC risk and risk of mortality by competing causes. In the German randomized Lung Screening Intervention Trial (LUSI), we measured growth/differentiation factor-15 (GDF-15), interleukin-6 (IL-6), C-reactive protein (CRP) and N-terminal pro-brain natriuretic protein (NT-proBNP), in blood serum samples collected at start of the trial. Participants in the computed tomography (CT)-screening arm also had a pulmonary function test. Regression models were used to examine these markers as predictors for impaired lung function, LC risk and mortality due to LC or other causes, independently of age, sex and smoking history. Our models showed increases in LC risk among participants with elevated serum levels of GDF-15 [odds ratio (OR)Q4-Q1 =2.47, 95% confidence interval (CI): 1.49-4.26], IL-6 [ORQ4-Q1 =2.36 (1.43-4.00)] and CRP [ORQ4-Q1 =1.81 (1.08-2.75)]. Likewise, proportional hazards models showed increased risks for LC-related mortality, hazard ratio (HR)Q4-Q1 of 4.63 (95% CI: 2.13-10.07) for GDF-15, 3.56 (1.72-7.37) for IL-6 and 2.34 (1.24-4.39) for CRP. All four markers were associated with increased risk of mortality by causes other than LC, with strongest associations for GDF-15 [HRQ4-Q1 =3.04 (2.09-4.43)] and IL-6 [HRQ4-Q1 =2.98 (2.08-4.28)]. Significant associations were also observed between IL-6, CRP, GDF-15 and impaired pulmonary function [chronic obstructive pulmonary disease (COPD), preserved ratio impaired spirometry (PRISm)]. Multi-marker models identified GDF-15 and IL-6 as joint risk predictors for risk of LC diagnosis, without further discrimination by CRP or NT-proBNP. A model based on age, sex, smoking-related variables, GFD-15 and IL-6 provided moderately strong discrimination for prediction of LC diagnoses within 9 years after blood sampling [area under the curve (AUC) =74.3% (57.3-90.2%)], compared to 67.0% (49.3-84.8%) for a model without biomarkers. For mortality by competing causes, a model including biomarkers resulted in an AUC of 76.2% (66.6-85.3%)], compared to 70.0% (60.9-77.9%) a model including age, sex and smoking variables. Serum GDF-15 and IL-6 may be useful indicators for estimating risks for LC and competing mortality among long-term smokers participating in LC screening, to optimize LC screening strategies.

Abstract B069: Lung cancer risk in women and racial minorities and genetic variants of UGT genes

Abstract The major research focus of this project is the identification of genetic variants involved in disparities in carcinogen metabolism and risk for cancer. Specifically, this research focuses on the identification of genetic variants in carcinogen metabolism genes, that increase lung cancer risk, particularity when the risk differs between men and women or by racial groups. Although cigarette smoking causes the vast majority of lung cancers, most lifetime smokers do not develop this disease. Many studies suggest that women have greater susceptibility than men for lung cancer, and that risk varies by racial groups. Genetic variation in tobacco carcinogen-metabolizing enzymes could give details as to why only some smokers develop lung cancer and why women or certain racial groups may be at a greater risk. Genetic changes have been shown to vary significantly between individuals of different races, which could contribute to racial disparities in cancer risk. Uridine glucuronosyltransferase (UGT) genes detoxify many carcinogens found in tobacco, so variants in UGT genes could explain differences in lung cancer risk among smokers. Many genetic association studies of UGT genes and lung cancer risk have been performed to identify alleles (SNPs and Copy Number Variants) in UGT genes that increase risk for lung cancer, and to determine if some variants display a gender or racial-specific association with this cancer. cBioPortal provides gene-based visualizations and analyses, so that users can find altered genes and/or networks within a study of interest or across all cancer studies. cBioPortal is a web application platform that facilitates data exploration and analysis through the use of a variety of visualization and analytical tools using populations of cancer cases and controls. cBioPortal has been utilized in this study to visualize variations in UGT genes across many lung cancer data sets. A copy number variant that deletes the entire UGT2B17 gene (which metabolizes the lung cancer carcinogen, NNAL) is a particular focus in this study using data from cBioPortal, as well as common copy number alterations (amplifications) in UGT3A1 and UGT3A2. Citation Format: James W. Gallagher, Talayshia Vicks, Carla J. Gallagher. Lung cancer risk in women and racial minorities and genetic variants of UGT genes [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B069.

Racial/Ethnic disparities in exposure to neighborhood violence and lung cancer risk in Chicago

BackgroundDespite the lower prevalence and frequency of smoking, Black adults are disproportionately affected by lung cancer. Exposure to chronic stress generates heightened immune responses, which creates a cell environment conducive to lung cancer development. Residents in poor and segregated neighborhoods are exposed to increased neighborhood violence, and chronic exposure to violence may have downstream physiological stress responses, which may explain racial disparities in lung cancer in predominantly Black urban communities. MethodsWe utilized retrospective electronic medical records of patients who underwent a screening or diagnostic test for lung cancer at an academic medical center in Chicago to examine the associations between lung cancer diagnosis and individual characteristics (age, gender, race/ethnicity, and smoking status) and neighborhood-level homicide rate. We then used a synthetic population to estimate the neighborhood-level lung cancer risk to understand spatial clusters of increased homicide rates and lung cancer risk. ResultsOlder age and former/current smoking status were associated with increased odds of lung cancer diagnosis. Hispanic patients were more likely than White patients to be diagnosed with lung cancer, but there was no statistical difference between Black and White patients in lung cancer diagnosis. The odds of being diagnosed with lung cancer were significantly higher for patients living in areas with the third and fourth quartiles of homicide rates compared to the second quartile of homicide rates. Furthermore, significant spatial clusters of increased lung cancer risk and homicide rates were observed on Chicago's South and West sides. ConclusionsNeighborhood violence was associated with an increased risk of lung cancer. Black residents in Chicago are disproportionately exposed to neighborhood violence, which may partially explain the existing racial disparity in lung cancer. Incorporating neighborhood violence exposure into lung cancer risk models may help identify high-risk individuals who could benefit from lung cancer screening.

Risk factors for early-onset lung cancer in Korea: analysis of a nationally representative population-based cohort.

We examined the associations of socioeconomic factors, health behaviors, and comorbidities with early-onset lung cancer. The study included 6,794,287 individuals aged 20-39 years who participated in a Korean national health check-up program from 2009 to 2012. During the follow-up period, 4,684 participants developed lung cancer. Multivariable Cox regression analysis was used to estimate the independent associations of potential risk factors with incident lung cancer. Older age (multivariable hazard ratio [mHR], 1.13; 95% confidence interval [CI], 1.12 to 1.14) and female sex (mHR, 1.62; 95% CI, 1.49 to 1.75) were associated with increased lung cancer risk. Current smoking was also associated with elevated risk (<10 pack-years: mHR, 1.12; 95% CI, 1.01 to 1.24; ≥10 pack-years: mHR, 1.30; 95% CI, 1.18 to 1.45), but past smoking was not. Although mild alcohol consumption (<10 g/day) was associated with lower lung cancer risk (mHR, 0.92; 95% CI, 0.86 to 0.99), heavier alcohol consumption (≥10 g/day) was not. Higher income (highest vs. lowest quartile: mHR, 0.86; 95% CI, 0.78 to 0.94), physical activity for at least 1,500 metabolic equivalent of task-min/wk (vs. non-exercisers: mHR, 0.83; 95% CI, 0.69 to 0.99) and obesity (vs. normal weight: mHR, 0.89; 95% CI, 0.83 to 0.96) were associated with lower lung cancer risk, whereas metabolic syndrome was associated with increased risk (mHR, 1.13; 95% CI, 1.03 to 1.24). In young adults, age, female sex, smoking, and metabolic syndrome were risk factors for early-onset lung cancer, while high income, physical activity, and obesity displayed protective effects.

Pathogenic germline variants in BRCA1 and TP53 increase lung cancer risk in Chinese.

Multiple studies have identified pathogenic germline variants in cancer susceptibility genes (CSGs) in Chinese lung cancer patients; however, accurate assessment of these variants' contributions to cancer predisposition is always hampered by the absence of data on the prevalence of these variants in the general population. It is necessary to conduct a large-scale case-control study to identify CSGs that significantly increase the risk of lung cancer. We performed targeted sequencing of a CSGs panel in 1117 lung cancer patients and 16,327 controls from the general Chinese population. In comparison to controls, lung cancer patients had a considerably higher prevalence of pathogenic and likely pathogenic (P/LP) variations. Among lung cancer patients, 72% of P/LP variants carriers did not have a family cancer history, who would be ignored if germline testing was only provided for patients meeting family history-based criteria. Furthermore, compared to individuals with late-onset lung cancer, patients with early-onset lung cancer had a considerably higher prevalence of P/LP variations. With odds ratios (ORs) ranging from 4-fold (BRCA1: OR, 4.193; 95%CI, 1.382-10.768) to 29-fold (TP53: OR, 29.281; 95%CI, 1.523-1705.506), P/LP variants in the BRCA1 and TP53 genes were discovered to be strongly related to increased lung cancer risk. Additionally, with ORs ranging from 7.322-fold to infinity, we discovered 23 variations previously categorized as non-P/LP variants were highly enriched in lung cancer patients. Our findings indicated that P/LP variants in BRCA1 and TP53 conferred increased risk of lung cancer in Chinese.

The blockage signal for PD-L1/CD274 gene variants and their potential impact on lung carcinoma susceptibility

BackgroundThe programmed death-ligand 1 (PD-L1/CD274) gene plays a key function in suppressing anti-tumor immunity through binding to its receptor PD-1 on stimulated T lymphocytes. However, robust associations among diverse populations and lung susceptibility remain unclear. The tentative purpose of this research is to investigate whether PD-L1/CD274 polymorphisms modulate susceptibility to lung carcinoma using totalitarian techniques, including genetic analysis, and sophisticated bioinformatic methods. MethodsPD-L1/CD274 (rs822336, rs2297136, and rs4143815) variants were genotyped in 126 lung carcinoma cases and 117 healthy controls using tetra-primer ARMS-PCR. Logistic regression and bioinformatics analyses assessed genetic associations. ResultsThe rs2297136 GA genotype significantly increased lung cancer risk by 3.7-fold versus GG genotype (OR 3.69, 95 % CI 1.39–9.81, p = 0.016), with the minor A allele also increasing risk (OR 1.47, p = 0.044). In contrast, the rs4143815 CC genotype was associated with 70 % decreased cancer risk versus GG (OR 0.30, 95 % CI 0.11–0.87, p = 0.012), although the minor C allele itself was not significant. The rs822336 variant showed no association. Haplotype and multivariate analyses supported these findings. In silico predictions suggested functional impacts on PD-L1 expression and activity. ConclusionsThis study identified novel associations between PD-L1/CD274 polymorphisms and susceptibility to lung cancer in Egyptians. The rs2297136 variant increased risk while the rs4143815 variant conferred protection, highlighting the PD-1/PD-L1 axis as a potential biomarker and therapeutic target in lung oncogenesis. Replication in larger cohorts and functional studies are warranted.

The association between sleep duration and lung cancer: a meta-analysis.

The link between sleep duration and lung cancer risk has been suggested by some epidemiological studies. This meta-analysis was performed to further understand this relationship. MEDLINE and EMBASE entries up to December 2022 were searched for eligible publications. A random effects model was used to calculate pooled relative risks (RRs) with 95% confidence intervals (95% CIs). Publication bias was estimated using Begg's and Egger's regression asymmetry test. The meta-analysis included 11 studies (including 10 cohort studies and 1 case-control study). The pooled adjusted RRs were 1.13 (95% CI: 1.03-1.24) for short sleep duration and 1.21 (95% CI: 1.07-1.37) for long sleep duration. The findings of this meta-analysis suggested that both short and long sleep duration are associated with an increase in lung cancer risk. These findings need to be corroborated through large-scale prospective studies.

Associations between Longer Leukocyte Telomere Length and Increased Lung Cancer Risk among Never Smokers in Urban China.

The complex relationship between measured leukocyte telomere length (LTL), genetically predicted LTL (gTL), and carcinogenesis is exemplified by lung cancer. We previously reported associations between longer pre-diagnostic LTL, gTL, and increased lung cancer risk among European and East Asian populations. However, we had limited statistical power to examine the associations among never smokers by gender and histology. To investigate further, we conducted nested case-control analyses on an expanded sample of never smokers from the prospective Shanghai Women's Health Studies (798 cases and 792 controls) and Shanghai Men's Health Studies (161 cases and 162 controls). We broke the case-control matching and used multivariable unconditional logistic regression models to estimate the ORs and 95% confidence intervals (CI) of incident lung cancer and adenocarcinoma (LUAD), in relation to LTL measured using quantitative PCR and gTL determined using a polygenic score. In addition, we conducted Mendelian randomization (MR) using MR-PRESSO. We found striking dose-response relationships between longer LTL and gTL, and increased lung cancer risk among never-smoking women (P trendLTL = 4×10-6; P trendgTL = 3×10-4). Similarly, among never-smoking men, longer measured LTL was associated with over triple the risk compared with those with the shortest (OR, 3.48; 95% CI, 1.85-6.57). The overall results were similar for LUAD among women and men. MR analyses supported causal associations with LUAD among women (OR1 SD gTL, 1.19; 95% CI, 1.03-1.37; P = 0.03). Longer pre-diagnostic LTL is associated with increased lung cancer risk among never smokers. Our findings firmly support the role of longer telomeres in lung carcinogenesis.