Increased Risk Of Lung Cancer Research Articles

Investigating the Relationship Between Exposure to Cadmium and Lung Cancer Risk: A Systematic Review and Meta-analysis

Introduction: Lung cancer is the second most common cancer in the world. Smoking occupational andenvironmental exposures are the most important causes of lung cancer. Cadmium is known as a humancarcinogen due to its ability to increase lung cancer risk. This study estimates the general results of allstudies on the relationship between cadmium and lung cancer. Material and Methods: In the present study, studies that evaluated the relationship between cadmium andlung cancer until May 2022 were searched and retrieved. From the funnel plot to determine the existenceof diffusion skew, from the statistical tests Chi-squared test (x2) and I2 to determine heterogeneity,from the meta-regression method to identify the root of heterogeneity, and from the sensitivity analysisapproach to identify the effect of each study on the result, it was generally used. This study performed allanalyses with Stata statistical software version 15. Results: In this study, it was observed that the chance of developing lung cancer compared to the basegroup, in the people exposed to a higher dose than the base level of cadmium is equal to 1.31 (95% CI:1.06-1.62; p-value = 0.024), which is statistically significant. Based on Egger’s test (p-value = 0.178) andBegg’s (p-value = 0.276), no diffusion bias was observed in this study. Conclusion: ccording to the final results of this review research, exposure to cadmium leads to a 31%increase in lung cancer risk, which is statistically significant. Therefore, cadmium is a risk factor for lung cancer.

Association of alcohol with lung cancer risk in men with different growth hormone receptor genotypes

ObjectiveTo test whether genetic variants of the growth hormone receptor gene (GHR) modulate the effect of lifestyle variables on lung cancer (LC) risk. Materials and methodsThis population-based cohort study involved 6,439 men from the Japan-Hawaii Cancer study drawn from the Kuakini Honolulu Heart Program who were cancer-free at baseline examination (1965–1968; age 45–68 years) and followed-up until December 1999. We determined the association of GHR SNP rs4130113 genotypes GHR-AA (common allele A homozygotes) and GHR-G (minor allele G carriage) with alcohol drinking, BMI, physical activity and cigarette smoking in relation to LC and non-small cell LC (NSCLC). Results were expressed as hazard ratios and 95 % CIs estimated from Cox proportional hazard models. ResultsOver mean 26.7 ± 7.4 SD years follow-up, 190 LC cases, including 133 NSCLC cases, were diagnosed. After adjusting for age, education, alcohol intake, BMI, physical activity, cigarette smoking, green tea consumption and dietary saturated fat, main-effect Cox models showed that compared with GHR-AA, GHR-G was associated with protection against LC: HR = 0.75 (95 % CI, 0.56–1.00). Full Cox models showed GHR-G interacted with alcohol intake only (β = 1.171; p = 0.0003; drinks per week: β = 0.279; P = 0.0025). Stratified analyses showed that for GHR-AA, drinkers had reduced LC risk (HR = 0.53; 95 % CI, 0.34–0.84), and that <2 drinks/week had the strongest protection (HR = 0.39; 95 % CI, 0.18–0.84). In contrast, for GHR-G, alcohol drinkers had increased LC risk (HR = 1.74; 95 % CI, 1.11–2.75) which was dose-dependent (P for trend = 0.003). Results for NSCLC were similar. ConclusionIn men with the GHR-AA genotype, alcohol drinking at a low dose poses significantly less risk of LC compared with non-drinkers and higher alcohol consumption., the overall relationship being U-shaped. In contrast, in GHR minor allele carriers, alcohol posed a progressively greater risk of LC as amount consumed increased

The immune cells causative role in lung cancer: Mendelian randomization study

BackgroundsLung cancer (LC) is the leading cause of cancer-related deaths in China, with its incidence and mortality rates rising annually. Various studies have demonstrated disparities in immune cell counts and profiles between LC patients and healthy individuals. However, the existence of a causal link remains largely uncertain. To explore the potential causal association between immune cells and LC risk, a Mendelian randomization (MR) approach was employed.MethodsEmploying immune cell genome-wide association study (GWAS) data from a public database (n = 731 subjects) and Lung Cancer Genome Research Consortium's GWAS dataset (n = 492,803 participants), unconventional genetic loci remarkably associated with the significant abundance of 731 types of immune cells were extracted according to preset threshold points as instrumental variables. The primarily analytical strategy involved the inverse variance weighting (IVW) method, with the effect size estimates expressed as odds ratio (OR) and 95% CI. The robustness of the findings was assessed through a leave-one-out sensitivity analysis, heterogeneity test, horizontal gene pleiotropy test, MR-PRESSO and MR-Egger.ResultsThe MR analysis identified a significant association between 18 distinct immune cell types and lung cancer risk. MR analysis revealed that 7 types of immune cells, including CD20 on IgD − CD38 − B cell, CD20 on switched memory B cell, IgD on IgD + CD24 + B cell, BAFF − R on IgD − CD38 + B cell, CD39 + resting CD4 regulatory T cell Absolute Count, CD127 on CD45RA + CD4 + T cell, CD8 on Effector Memory CD8 + T cell, displayed a protective effect against lung cancer development. Conversely, 11 other immune cells populations were positive associated with an increased lung cancer risk. In contrast, reverse MR analysis indicated that the lung cancer risk was linked to 11 immune cells, with 2 types of immune cells (CD25 on IgD − CD27 − B cell, CD4 + T cell %leukocyte) showing a are positive correlation with cancer development, whereas 9 types of immune cells appeared to be inversely regulated. These findings collectively imply that specific immune cell populations may play critical roles in either promoting or suppressing the initiation and progression of lung cancer.ConclusionThe findings of this study offer fresh insights into the underlying biological mechanisms governing lung cancer development, thereby opening new avenues for future research in the domain of LC. The identification of specific immune cell subsets with protective or promoting roles provides crucial leads for preventive and therapeutic strategies. These insights have the potential to enhance early detection methods and inform the development of more effective treatment approaches, ultimately benefiting patient outcomes and improving the overall management of lung cancer.

The burden of lung cancer attributable to ambient PM2.5 exposure: a systematic literature review

Abstract Background Lung cancer is recognized as one of the most common causes of cancer morbidity and mortality worldwide and is the second cause of death with highest years of life lost in highly developed regions. Ambient exposure to particulate matter (PM2.5) is the leading global environmental risk factor. Long-term exposure to PM2.5 is associated with several health outcomes, including lung cancer, ischemic heart disease, and chronic obstructive pulmonary disease. Aim To review and estimate the impact attributable to PM2.5 exposure due to lung cancer. Methods A systematic review and a meta-analysis were conducted to determine whether long-term exposure to PM2.5 increases the risk of lung cancer and to derive exposure-response relationships between PM2.5 and lung cancer. The literature search was performed in databases (i.e., Pubmed/Scopus) and studies published from January 1, 2010 onwards were considered. Studies describing the association between long-term exposure to the pollutant under research and the incidence, prevalence, and mortality of lung cancer, considering a relative measure of association were included, with no restriction in geographical area. Results In the literature review, 2215 articles were considered for the first step of data synthesis, all articles were screened, considering the screening of titles (first step), abstracts (second step) and full-text (third step) considering the inclusion criteria. In a second step the data was extracted from the included articles (n = 129) and considering the variables related to the characteristics of the study and the study population, exposure, and outcome measurement, and details of risk of bias assessment. Conclusions These findings provide data to synthesize effect size estimates using a Meta-Regression - Bayesian, Ensemble, Regularized, Trimmed (MR-BRT) model, important to provide evidence data on the impact of air pollution on human health, which is crucial for decision-making. Key messages • Long-term exposure to PM2.5 increases lung cancer risk so the estimating of the impact of the exposure is an urgent need to provide evidence-based data for air quality improvement. • Meta-analysis aims to establish a relation between PM2.5 exposure and the burden of lung cancer.

Bias analysis on socioeconomic status and lung cancer in a pooled international case-control study

Abstract Background Low socioeconomic status (SES) groups showed increased lung cancer risks even after adjustment for smoking habits and other exposures to lung carcinogens. Although several biases were often indicated and discussed, only few studies quantified the impact of potential biases. Methods We conducted a bias analysis on the association of lung cancer and SES using data from the SYNERGY project, including 12 case-control studies with 18 study centres from Europe and Canada (16,550 cases, 20,147 controls). SES in quartiles was derived from the International Socio-Economic Index of occupational status (ISEI). Odds ratios (OR) with 95% confidence intervals (CI) were estimated by logistic regression adjusting for age, study centre, and smoking. In addition, we estimated natural direct SES effects and natural indirect smoking effects by inverse odds ratio weighting. In a multiple quantitative bias analysis, we considered impacts of misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by a protective genetic factor, and created 95% simulation intervals (SI) by bootstrap. All analyses were stratified by sex. Results Adjustment for smoking as well as natural effects estimation showed that nearly half of lung cancer risks of lower SES groups in men and up to one third in women were attributable to smoking. Consideration of all types of bias reduced lung-cancer risks in the fully adjusted logistic regression models, with the strongest impact by selection bias: For the 4th versus 1st (highest) ISEI quartile OR decreased from 1.83 (1.69-1.98 CI) to 1.50 (1.30-1.73 SI) in men, and OR 1.48 (1.27-1.72 CI) to 1.20 (0.96-1.53 SI) in women. Conclusions Smoking is the main target for prevention of lung cancer, along with occupational and environmental exposures, in particular in lower SES groups. This finding remains, though our analysis revealed reduced lung-cancer risks of lower SES groups after multiple bias adjustment. Key messages • Impact of potential biases was quantified in the association of SES and lung cancer. • Lung cancer risks were partially attributable to smoking and multiple biases.

Allostatic Load, Cigarette Smoking, and Lung Cancer Risk.

Background: Allostatic load (AL) is a biomarker of chronic stress associated with various chronic diseases. No study has evaluated the relationship between AL and lung cancer risk. Methods: To address this gap, we analyzed the association between AL and the development of lung cancer in 344,380 participants from the UK Biobank. Results: During the follow-up period from 2006 to 2020, 2517 participants were diagnosed with incident lung cancer. Participants who developed lung cancer had significantly higher AL compared to cancer-free controls (mean: 3.49 vs. 2.87, p < 0.001). In the multivariate analysis, a marginally significant association was observed between higher AL and increased lung cancer risk (per one AL unit: Hazard Ratio [HR] = 1.02, 95% Confidence Interval [CI]: 0.99, 1.04). In the categorical analysis, individuals with high AL (AL > 2) had a 15% higher risk of lung cancer compared to those with low AL (AL ≤ 2) (HR = 1.15, 95% CI: 1.05, 1.25). Stratified analyses revealed that this increased risk was only observed in former (HR = 1.38, 95% CI: 1.06, 1.43) and current smokers (HR = 1.25, 95% CI: 1.10, 1.42) but not in never-smokers (HR = 0.93, 95% CI: 0.74, 1.17). Moreover, we found that demographics, socioeconomics, and other health behaviors could modify the risk association. Finally, among cigarette smoking-related variables, a significant trend of increasing AL was observed with higher pack-years, longer smoking duration, earlier age of smoking initiation, and later age of smoking cessation. Conclusions: These findings suggest that higher AL is associated with an increased risk of lung cancer. The results need to be further confirmed in additional studies.

Abstract A019: Dietary polyphenols and the risk of lung cancer in the prospective Southern Community Cohort Study

Abstract Objective: We examined total polyphenol intake and intake of polyphenol classes and subclasses with risk of lung cancer in the Southern Community Cohort Study (SCCS). Background: In the US, lung cancer incidence is highest in the south and among underrepresented and underserved populations. Diet is strongly associated with the risk of developing cancer, including lung cancer. Polyphenols, commonly found in plant-based foods, are biologically active compounds with antioxidant and other properties. Several population-based studies have found that higher intakes of some polyphenols were associated with a decreased risk of lung cancer, but this has not been studied in predominantly Black or low-income populations, nor have polyphenol classes and subclasses been studied extensively. Methods: The SCCS is a large, prospective cohort study established in 2002-2009 to study the causes of cancer disparities in 12 southern states. Two-thirds of the cohort are Black and over 50% have an annual household income less than $15,000. Diagnosis of lung cancer was obtained from state cancer registries and death records. Polyphenol intakes derived from a food frequency questionnaire assessing diet in the previous year were adjusted for total energy intake and grouped into quintiles. Cox proportional hazard models adjusted for potential confounders were used to estimate hazard ratios and 95% confidence intervals to determine associations between polyphenol intakes and lung cancer risk. Multiple imputation was performed to account for participants with incomplete information. After exclusions, analyses included 71,569 participants, including 1,484 incident lung cancer cases. Results: Total polyphenols were associated with a statistically significant increased risk of lung cancer (HR, 1.25; 95% CI, 1.04-1.51; P=0.01, comparing the highest to lowest intake quintile). Additionally, three subclasses (phenolic acids, hydroxycinnamic acids, alkylmethoxyphenols) were associated with a similarly statistically significant increased risk of lung cancer. Most associations were similar between Black and White individuals but were largely only statistically significant among Black participants and there was no significant interaction by race. In stratified analysis by smoking status, the associations were primarily present among current and former smokers. Caffeinated or decaffeinated coffee consumption was a major contributor to intake of total polyphenols, phenolic acids, hydroxycinnamic acids, and alkylmethoxyphenols for SCCS participants overall. Conclusions: Total polyphenols and three subclasses of polyphenols were unexpectedly associated with increased lung cancer risk. Further studies should be conducted to evaluate whether some polyphenols may have an adverse effect on lung carcinogenesis, particularly among individuals who smoke. Citation Format: Grace Xu, Heather Munro, Danxia Yu, Qi Dai, Martha Shrubsole. Dietary polyphenols and the risk of lung cancer in the prospective Southern Community Cohort Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A019.

Re-visiting the association between antidepressant use and the risk of lung cancer.

Observational studies suggest a potential correlation between antidepressants and increased lung cancer risks. However, existing studies are limited to small sample sizes, unadjusted covariates especially smoking status, and unclear exposure duration. We performed a large-scale retrospective cohort study to re-examine the association. We analyzed non-smokers and smokers separately to eliminate the confounding effect of smoking status. We found patients with long-term antidepressant use were at a lower risk of lung cancer in both smokers and non-smokers (odds ratio (OR), 0.61; 95% CI: 0.46-0.80, OR: 0.75; 95% CI: 0.65-0.86). None of the antidepressants was associated with an increased lung cancer risk.

Dietary Interventions for Cancer Prevention: An Update to ACS International Guidelines.

Cancer, the second leading cause of death worldwide, demands the identification of modifiable risk factors to optimize its prevention. Diet has emerged as a pivotal focus in current research efforts. This literature review aims to enhance the ACS guidelines on diet and cancer by integrating the latest findings and addressing unresolved questions. The methodology involved an advanced PubMed search with specific filters relevant to the research topic. Topics covered include time-restricted diet, diet quality, acid load, counseling, exercise and diet combination, Mediterranean diet, vegetarian and pescetarian diets, weight loss, dairy consumption, coffee and tea, iron, carbohydrates, meat, fruits and vegetables, heavy metals, micronutrients, and phytoestrogens. The review highlights the benefits of the Mediterranean diet in reducing cancer risk. Adherence to overnight fasting or carbohydrate consumption may contribute to cancer prevention, but excessive fasting may harm patients' quality of life. A vegetarian/pescetarian diet is associated with lower risks of general and colorectal cancer compared to a carnivorous diet. High heme and total iron intake are linked to increased lung cancer risk, while phytoestrogen intake is associated with reduced risk. Coffee and tea have a neutral impact on cancer risk. Finally, the roles of several preventive micronutrients and carcinogenic heavy metals are discussed.

The Risk of Lung Cancer in Rheumatoid Arthritis and Rheumatoid Arthritis-Associated Interstitial Lung Disease.

We aimed to evaluate lung cancer risk in patients with rheumatoid arthritis (RA) and RA-interstitial lung disease (ILD). We performed a retrospective, matched cohort study of RA and RA-ILD within the Veterans Health Administration (VA) between 2000 and 2019. Patients with RA and RA-ILD were identified with validated administrative-based algorithms, then matched (up to 1:10) on age, gender, and VA enrollment year to individuals without RA. Lung cancers were identified from a VA oncology database and the National Death Index. Conditional Cox regression models assessed lung cancer risk adjusting for race, ethnicity, smoking status, Agent Orange exposure, and comorbidity burden among matched individuals. Several sensitivity analyses were performed. We matched 72,795 patients with RA with 633,937 patients without RA (mean age 63 years; 88% male). Over 4,481,323 patient-years, 17,099 incident lung cancers occurred. RA was independently associated with an increased lung cancer risk (adjusted hazard ratio [aHR] 1.58 [95% confidence interval (CI) 1.52-1.64]), which persisted in never smokers (aHR 1.65 [95% CI 1.22-2.24]) and in those with incident RA (aHR 1.54 [95% CI 1.44-1.65]). Compared to non-RA controls, prevalent RA-ILD (n = 757) was more strongly associated with lung cancer risk (aHR 3.25 [95% CI 2.13-4.95]) than RA without ILD (aHR 1.57 [95% CI 1.51-1.64]). Analyses of both prevalent and incident RA-ILD produced similar results (RA-ILD vs non-RA aHR 2.88 [95% CI 2.45-3.40]). RA was associated with a >50% increased risk of lung cancer, and those with RA-ILD represented a particularly high-risk group with an approximate three-fold increased risk. Increased lung cancer surveillance in RA, and especially RA-ILD, may be a useful strategy for reducing the burden posed by the leading cause of cancer death.

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.

According to a NIH study, Lung cancer among individuals who have never smoked is more prevalent in women and occurs at an earlier age than in smokers. The rise in lung cancer rates among female non-smokers might be linked to radon inhalation and should be further investigated. Our theory is based on the differences in radon exposure between males and females, which can be attributed to the variations in time spent indoors versus outdoors. Over the past few years, the smoking rates have shown a steady decline in the United States and other developed countries. This decrease in smoking prevalence has led to a new shift in the primary risk factors associated with lung cancer. Although tobacco smoke historically served as the primary cause of lung cancer, the reduction in smoking rates has allowed other risk factors, such as radon exposure, to come to the forefront. Given that women in certain countries, on average, might spend more time indoors compared to men, they are potentially exposed to higher levels of radon. This increased exposure could explain the rising rates of lung cancer among female non-smokers. The theory is still in its nascent stages and requires further research and validation. However, if proven correct, it could significantly alter our understanding of lung cancer risk factors and lead to new prevention. It is therefore crucial to expedite the review and publication of this theory, given its potential implications for public health.

Stem cells, Notch-1 signaling, and oxidative stress: a hellish trio in cancer development and progression within the airways. Is there a role for natural compounds?

Notch-1 signaling plays a crucial role in stem cell maintenance and in repair mechanisms in various mucosal surfaces, including airway mucosa. Persistent injury can induce an aberrant activation of Notch-1 signaling in stem cells leading to an increased risk of cancer initiation and progression. Chronic inflammatory respiratory disorders, including chronic obstructive pulmonary disease (COPD) is associated with both overactivation of Notch-1 signaling and increased lung cancer risk. Increased oxidative stress, also due to cigarette smoke, can further contribute to promote cancer initiation and progression by amplifying inflammatory responses, by activating the Notch-1 signaling, and by blocking regulatory mechanisms that inhibit the growth capacity of stem cells. This review offers a comprehensive overview of the effects of aberrant Notch-1 signaling activation in stem cells and of increased oxidative stress in lung cancer. The putative role of natural compounds with antioxidant properties is also described.

Absence of lung tumor promotion with reduced tumor size in mice after inhalation of copper welding fumes.

Welding fumes are a Group 1 (carcinogenic to humans) carcinogen as classified by the International Agency for Research on Cancer. The process of welding creates inhalable fumes rich in iron (Fe) that may also contain known carcinogenic metals such as chromium (Cr) and nickel (Ni). Epidemiological evidence has shown that both mild steel (Fe-rich) and stainless steel (Fe-rich + Cr + Ni) welding fume exposure increases lung cancer risk, and experimental animal data support these findings. Copper-nickel (CuNi) welding processes have not been investigated in the context of lung cancer. Cu is intriguing, however, given the role of Cu in carcinogenesis and cancer therapeutics. This study examines the potential for a CuNi fume to induce mechanistic key characteristics of carcinogenesis in vitro and to promote lung tumorigenesis, using a two-stage mouse bioassay, in vivo. Male A/J mice, initiated with 3-methylcholanthrene (MCA; 10 µg/g), were exposed to CuNi fumes or air by whole-body inhalation for 9 weeks (low deposition-LD and high deposition-HD) and then sacrificed at 30 weeks. In BEAS-2B cells, the CuNi fume-induced micronuclei and caused DNA damage as measured by γ-H2AX. The fume exhibited high reactivity and a dose-response in cytotoxicity and oxidative stress. In vivo, MCA/CuNi HD and LD significantly decreased lung tumor size and adenomas. MCA/CuNi HD exposure significantly decreased gross-evaluated tumor number. In summary, the CuNi fume in vitro exhibited characteristics of a carcinogen, but in vivo, the exposure resulted in smaller tumors, fewer adenomas, less hyperplasia severity, and with HD exposure, less overall lung lesions/tumors.

CD147 TagSNP is associated with the vulnerability to lung cancer in the Chinese population: a case–control study

BackgroundLung cancer, with its high morbidity and mortality, presents a major significant public health challenge. CD147, linked to cancer progression and metastasis, is a promising therapeutic target, including for lung cancer. The genetic variation may influence the expression of the gene and consequently the risk of lung cancer. This study aims to investigate single nucleotide polymorphisms (SNPs) in CD147 to understand their association with the risk of developing lung cancer in the Han Chinese population.MethodsA hospital-based case–control investigation was conducted, enrolling 700 lung cancer patients and 700 cancer-free controls. TagSNPs were selected using Haploview v4.2, and genotype data from the 1000 Genomes Project database were utilized. The selected SNPs (rs28992491, rs67945626, and rs79361899) within the CD147 gene were evaluated using the improved multiple ligation detection reaction method. Statistical analysis included chi-square tests, logistic regression models, and interaction analyses.ResultsBaseline characteristics of the study population showed no significant differences in gender distribution between cases and controls, but there was a notable difference in smoking rates. No significant associations were found between the three TagSNPs and lung cancer susceptibility in the codominant model. However, stratification analyses revealed interesting findings. Among females, the rs79361899 AA/AG genotype was associated with an increased risk of lung cancer. In individuals aged ≥ 65 years old, the rs28992491 GG and rs79361899 AA genotypes were linked to a higher susceptibility. Furthermore, an interaction analysis demonstrated significant genotype × gender interactions in the rs79361899 recessive model, indicating an increased lung cancer risk in female carriers of the heterozygous or homozygous polymorphic genotype.ConclusionsCD147 polymorphisms play an important role in lung cancer development, particularly in specific subgroup of age and gender. These findings highlight the significance of incorporating genetic variations and their interactions with demographic factors in comprehending the intricate etiology of lung cancer.

Increased risk of subsequent primary lung cancer among female hormone-related cancer patients: A meta-analysis based on over four million cases.

The incidence rate of lung cancer in women has significantly increased over the past decade, and previous evidence has indicated a significant relationship between the elevated levels of sex hormones and the risk of lung cancer. Therefore, we hypothesized that female hormone-related cancer (FHRC) patients, including breast, endometrial, cervical, and ovarian cancer patients, may experience a higher risk of developing subsequent lung cancer. This meta-analysis aimed to identify the risk of lung cancer among FHRC patients compared to the general population. The PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI databases were searched up to May 11, 2022. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used to identify the risk of subsequent lung cancer after FHRC. Subgroup analyses based on the follow-up time and tumor type were also conducted. A total of 58 retrospective cohort studies involving 4,360,723 FHRC participants were included. The pooled results demonstrated that FHRC patients had a significantly increased risk of developing subsequent primary lung cancer (SIR=1.61, 95% CI: 1.48-1.76, P <0.001). Subgroup analysis revealed an obvious trend of increasing lung cancer risk over time (SIRs for <5years, ≥5years, ≥10years, ≥20years, and ≥30years after FHRC: 1.32, 1.59, 1.57, 1.68, and 1.95, respectively). In addition, subgroup analysis stratified by tumor type indicated an increased risk of developing subsequent lung cancer after breast (SIR=1.25, P <0.001), endometrial (SIR=1.40, P =0.019), cervical (SIR=2.56, P <0.001), and ovarian cancer (SIR=1.50, P =0.010). FHRC patients are more likely to develop lung cancer than the general population. Furthermore, the increased risk of subsequent primary lung cancer is more obvious with a longer survival time and is observed in all types of hormone-related cancer. International Platform of Registered Systematic Review and Meta-analysis Protocols: No. INPLASY202270044; https://inplasy.com/.

Non-Insulin Antidiabetic Agents and Lung Cancer Risk in Drug-Naive Patients with Type 2 Diabetes Mellitus: A Nationwide Retrospective Cohort Study.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), is associated with increased LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients, comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed the de-identified electronic health records of 1,040,341 T2DM patients treated between 2005 and 2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, were associated with significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

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 (&lt;0.05).

Adherence to the low-fat diet pattern reduces the risk of lung cancer in American adults aged 55 years and above: a prospective cohort study

ObjectivesThere is little evidence on the association between low-fat dietary patterns and lung cancer risk among middle-aged and older adults. To fill this gap, we comprehensively investigated the association of adherence to a low-fat diet (LFD) and intake of different fat components including saturated, monounsaturated, and polyunsaturated fatty acids with incidence of lung cancer and its subtypes [non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] among adults aged 55 years and older. DesignA prospective cohort study with a mean follow-up time of 8.8 years. Setting and participantsThis study used data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The study population included 98,459 PLCO participants age 55 and over at baseline who completed food frequency questionnaires providing detailed dietary information and had no history of cancer. MethodsDietary intake was assessed using a validated food frequency questionnaire at baseline. A LFD score was calculated based on fat, protein, and carbohydrate intake as a percentage of total calories. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LFD score and intake of fat components (in quartiles) and incident lung cancer and its subtypes over follow-up. Restricted cubic spline analyses were conducted to examine possible nonlinear relationships. Subgroup analyses were performed to evaluate potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. ResultsDuring a follow-up of 869,807.9 person-years, 1,642 cases of lung cancer were observed, consisting of 1,408 (85.75%) cases of NSCLC and 234 (14.25%) cases of SCLC. The highest versus the lowest quartiles of the LFD score were found to be associated with a reduced risk of lung cancer (HR, 0.76; 95% CI, 0.66−0.89), NSCLC (HR, 0.79; 95% CI, 0.67−0.93), and SCLC (HR, 0.59; 95% CI, 0.38−0.92). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of lung cancer as well as its subtypes. This risk reduction association for overall lung cancer was more pronounced in smokers (HR, 0.71; 95% CI, 0.60−0.84; P for interaction = 0.003). For fat components, high consumption of saturated fatty acids was associated with an increased lung cancer risk (HR, 1.35; 95% CI, 1.10–1.66), especially for SCLC (HR, 2.05; 95% CI, 1.20–3.53). No significant association was found between consumption of monounsaturated or polyunsaturated fatty acids and incident lung cancer and its subtypes. ConclusionsOur findings suggest that adherence to LFD may reduce the lung cancer risk, particularly in smokers; while high saturated fatty acids consumption may increase lung cancer risk, especially for SCLC, among middle-aged and older adults in the US population.