Associations between chronic obstructive pulmonary disease and ten common cancers: novel insights from Mendelian randomization analyses.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a significant global health issue, suspected to elevate the risk for various cancers. This study sought to discern whether COPD serves as a risk marker or a causative factor for prevalent cancers. METHODS: We employed univariable MR (UVMR) analyses to investigate the causal relationship between COPD and the top ten common cancers. Sensitivity analyses were performed to validate the main findings. Multivariable MR (MVMR) and two-step MR analyses were also conducted. False-discovery-rate (FDR) was used to correct multiple testing bias. RESULTS: The UVMR analysis demonstrated notable associations between COPD and lung cancer (odds ratio [OR] = 1.42, 95%CI 1.15-1.77, FDR = 6.37 × 10-3). This relationship extends to lung cancer subtypes such as squamous cell carcinoma (LUSC), adenocarcinoma (LUAD), and small cell lung cancer (SCLC). A tentative link was also identified between COPD and bladder cancer (OR = 1.53, 95%CI 1.03-2.28, FDR = 0.125). No significant associations were found between COPD and other types of cancer. The MVMR analysis that adjusted for smoking, alcohol drinking, and body mass index did not identify any significant causal relationships between COPD and either lung or bladder cancer. However, the two-step MR analysis indicates that COPD mediated 19.2% (95% CI 12.7-26.1%), 36.1% (24.9-33.2%), 35.9% (25.7-34.9%), and 35.5% (26.2-34.8%) of the association between smoking and overall lung cancer, as well as LUAD, LUSC, and SCLC, respectively. CONCLUSIONS: COPD appears to act more as a risk marker than a direct cause of prevalent cancers. Importantly, it partially mediates the connection between smoking and lung cancer, underscoring its role in lung cancer prevention strategies.

Circulating tumor cell detection may offer earlier diagnosis in patients suspected of asbestos-related lung cancer.

Asbestos-Related Lung Cancer (ARLC) presents ongoing diagnostic challenges despite improved imaging technologies. The long latency period, coupled with limited access to occupational and environmental data along with the confounding effects of smoking and other carcinogens adds complexity to the diagnostic process. Compounding these challenges is the absence of a specific histopathologic or mutational signature of ARLC. A correlation between PD-L1 expression and response to immune checkpoint inhibition has not yet been proven. Thus, new biomarkers are needed to allow accurate diagnoses of ARLC, to enable prognostication and to offer personalized treatments. Liquid biopsies, encompassing circulating DNA and circulating tumor cells (CTCs), have gained attention as novel diagnostic methods in lung cancer to screen high-risk populations including those exposed to asbestos. CTCs can be enumerated and molecularly profiled to provide predictive and prognostic information. CTC studies have not been undertaken in populations at risk of ARLC to date. The potential of CTCs to provide real-time molecular insight into ARLC biology may significantly improve the diagnosis and management of ARLC patients.

Cancer Incidence Rates in the US in 2016-2020 with Respect to Solar UVB Doses, Diabetes and Obesity Prevalence, Lung Cancer Incidence Rates, and Alcohol Consumption: An Ecological Study.

This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950-1969 and 1970-1794 as well as cancer incidence rates for the period 1998-2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, diabetes, and obesity prevalence near the 2016-2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin's lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal, and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus, diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing the risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in terms of overweight and obese individuals, which are associated with lower 25-hydroxyvitamin D concentrations and the generation of systemic inflammation, which is a risk factor for cancer. A dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore, cancer, would be one based mostly on whole plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce the risk of cancer.

Association between waterpipe smoking and lung cancer: a multicentre case-control study in Iran.

OBJECTIVES: This study investigated the association between lung cancer and waterpipe smoking, which is an emerging global public health concern. STUDY DESIGN: Multicentre case-control study. METHODS: This study included 627 cases and 3477 controls from the Iranian Study of Opium and Cancer (IROPICAN) study, which was conducted between 2017 and 2020. One frequency-matched control for each lung cancer patient was selected by age, gender and residential place; however, this study used controls of four cancer types in the analyses. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence intervals (CIs). Additional analyses were performed among 181 lung cancer cases and 2141 controls who were not cigarette smokers or opium or nass/pipe users. RESULTS: The odds of lung cancer were higher among waterpipe smokers than never-smokers (OR = 1.3, 95% CI: 1.0-1.7). Results showed a higher OR of lung cancer for those who smoked the waterpipe daily (OR = 2.1, 95% CI: 1.4-3.0), smoked more than two heads per day (OR = 2.7, 95% CI: 1.8-4.0), had smoked for >20 years (OR = 1.9, 95% CI: 1.3-2.7), smoked more than 20 head-years (OR = 2.8, 95% CI: 1.9-4.1) and initiated smoking before the age of 30 years (OR = 1.7, 95% CI: 1.1-2.5). The association was only statistically significant for squamous cell carcinomas (OR = 1.8, 95% CI 1.2-2.7). Furthermore, this study observed a higher OR of lung cancer among exclusive waterpipe smokers (OR = 2.3, 95% CI: 1.6, 3.5). CONCLUSIONS: Waterpipe smoking was associated with an increased risk of lung cancer. The association was stronger with higher frequency, duration and intensity of exposure to waterpipe smoking. The association increases in exclusive waterpipe smokers, which is likely due to controlling for residual confounding by cigarette smoking and opium consumption, and higher exposure levels in this subpopulation.

Global burden of mesothelioma attributable to occupational asbestos exposure in 204 countries and territories: 1990-2019.

Malignant mesothelioma, a rare and aggressive cancer primarily caused by occupational asbestos exposure, has a poor prognosis. This study leverages the Global Burden of Disease (GBD) 2019 dataset to analyze the burden of mesothelioma linked to occupational asbestos exposure from 1990 to 2019. The analysis includes the number of mesothelioma deaths and disability-adjusted life years (DALYs) attributable to occupational asbestos exposure, focusing on trends in age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life-year rate (ASDR) by year, age, sex, country, region, and Socio-demographic Index (SDI). In 2019, 91.7% of mesothelioma deaths and 85.2% of DALYs were attributable to occupational asbestos exposure, resulting in 26,820 (95% UI 24,312-28,622) deaths and 569,429 (95% UI 509,956-617,484) DALYs. Despite a decline in ASMR and ASDR from 1990 to 2019, the absolute number of deaths and DALYs almost doubled. The United States reported the highest number of mesothelioma deaths, while China had the highest number of DALYs. Age-specific mortality rates and DALYs decreased in the 25-74 age group but increased in the 75+ age group. In conclusion, occupational asbestos exposure remains the primary cause of mesothelioma worldwide, with an increasing number of deaths and DALYs. The highest incidence rates are observed in high-income areas, and rates are rising in low-income areas. It is crucial to raise awareness about the hazards of asbestos to reduce the global burden of mesothelioma linked to occupational exposure.

Airway hillocks are injury-resistant reservoirs of unique plastic stem cells.

Airway hillocks are stratified epithelial structures of unknown function1. Hillocks persist for months and have a unique population of basal stem cells that express genes associated with barrier function and cell adhesion. Hillock basal stem cells continually replenish overlying squamous barrier cells. They exhibit dramatically higher turnover than the abundant, largely quiescent classic pseudostratified airway epithelium. Hillocks resist a remarkably broad spectrum of injuries, including toxins, infection, acid and physical injury because hillock squamous cells shield underlying hillock basal stem cells from injury. Hillock basal stem cells are capable of massive clonal expansion that is sufficient to resurface denuded airway, and eventually regenerate normal airway epithelium with each of its six component cell types. Hillock basal stem cells preferentially stratify and keratinize in the setting of retinoic acid signalling inhibition, a known cause of squamous metaplasia2,3. Here we show that mouse hillock expansion is the cause of vitamin A deficiency-induced squamous metaplasia. Finally, we identify human hillocks whose basal stem cells generate functional squamous barrier structures in culture. The existence of hillocks reframes our understanding of airway epithelial regeneration. Furthermore, we show that hillocks are one origin of 'squamous metaplasia', which is long thought to be a precursor of lung cancer.

Radon and lung cancer: Current status and future prospects.

Beyond tobacco smoking, radon takes its place as the second most significant contributor to lung cancer, excluding hereditary and other biologically related factors. Radon and its byproducts play a pivotal role in exposing humans to elevated levels of natural radiation. Approximately 10-20 % of lung cancer cases worldwide can be attributed to radon exposure, leading to between 3 % and 20 % of all lung cancer-related deaths. Nevertheless, a knowledge gap persists regarding the association between radon and lung cancer, impeding radon risk reduction initiatives globally. This review presents a comprehensive overview of the current state of research in epidemiology, cell biology, dosimetry, and risk modeling concerning radon exposure and its relevance to lung cancer. It also delves into methods for measuring radon concentrations, monitoring radon risk zones, and identifying priorities for future research.

A nationwide case-referent study on elevated risks of adenocarcinoma lung cancer by long-term PM2.5 exposure in Taiwan since 1997.

BACKGROUND: The effects of long-term PM2.5 exposures since 1968 on adenocarcinoma lung cancer (AdLC) were not studied before. METHODS: This case-referent study used nationwide cancer registry data since 1997 and air pollution data since 1968 in Taiwan to estimate risks of 30-year PM2.5 exposures on AdLC. Cases were all AdLC, while references were all non-AdLC. Individuals' 30-year PM2.5 exposures were estimated by PM2.5 levels at their residence for 30 years prior their diagnosis dates. We applied multiple logistic regression analyses to estimate PM2.5 exposures on incidence rate ratios (IRRs) between cases and references, adjusting for sex, age, smoking, cancer stage, and EGFR mutation. RESULTS: Elevation in annual ambient PM2.5 concentrations since 1968 were associated with increase in annual age-adjusted AdLC incidence since 1997. AdLC incidences were higher among females, nonsmokers, the elderly aged above 65, cases of stages IIIB to IV, and EGFR mutation. Study subjects' PM2.5 exposures averaged at 33.7 ± 7.4 µg/m3 with 162 ± 130 high PM2.5 pollution days over 30 years. Multiple logistic models showed an increase in 10 µg/m3 of PM2.5 exposures were significantly associated with 1.044 of IRR between all AdLC and all non-AdLC cases during 2011-2020. Our models also showed that females and nonsmokers and adults less than 65 years had higher IRRs than their respective counterparts. Restricted analyses showed similar effects of PM2.5 exposures on IRRs between stage 0-IIIA and IIIB-IV cases and between EGFR+ and EGFR- cases. CONCLUSIONS: Long-term exposures to PM2.5 over 30 years were associated with elevated risks of AdLC against non-AdLC, regardless of gender, age, smoking status, cancer stage, or EGFR mutation.

A review of obstructive sleep apnea and lung cancer: epidemiology, pathogenesis, and therapeutic options.

Despite undeniable advances in modern medicine, lung cancer still has high morbidity and mortality rates. Lung cancer is preventable and treatable, and it is important to identify new risk factors for lung cancer, especially those that can be treated or reversed. Obstructive sleep apnea (OSA) is a very common sleep-breathing disorder that is grossly underestimated in clinical practice. It can cause, exacerbate, and worsen adverse outcomes, including death and various diseases, but its relationship with lung cancer is unclear. A possible causal relationship between OSA and the onset and progression of lung cancer has been established biologically. The pathophysiological processes associated with OSA, such as sleep fragmentation, intermittent hypoxia, and increased sympathetic nervous excitation, may affect normal neuroendocrine regulation, impair immune function (especially innate and cellular immunity), and ultimately contribute to the occurrence of lung cancer, accelerate progression, and induce treatment resistance. OSA may be a contributor to but a preventable cause of the progression of lung cancer. However, whether this effect exists independently of other risk factors is unclear. Therefore, by reviewing the literature on the epidemiology, pathogenesis, and treatment of lung cancer and OSA, we hope to understand the relationships between the two and promote the interdisciplinary exchange of ideas between basic medicine, clinical medicine, respiratory medicine, sleep medicine, and oncology.

Simulated galactic cosmic radiation-induced cancer progression in mice.

Prolonged manned space flight exposure risks to galactic comic radiation, has led to uncertainties in a variety of health risks. Our previous work, utilizing either single ion or multiple ion radiation exposure conducted at the NSRL (NASA Space Radiation Laboratory, Brookhaven, NY) demonstrated that HZE ion components of the GCR result in persistent inflammatory signaling, increased mutations, and higher rates of cancer initiation and progression. With the development of the 33-beam galactic cosmic radiation simulations (GCRsim) at the NSRL, we can more closely test on earth the radiation environment found in space. With a previously used lung cancer susceptible mouse model (K-rasLA-1), we performed acute exposure experiments lasting 1-2 h, and chronic exposure experiments lasting 2-6 weeks with a total dose of 50 cGy and 75 cGy. We obtained histological samples from a subset of mice 100 days post-irradiation, and the remaining mice were monitored for overall survival up to 1-year post-irradiation. When we compared acute exposures (1-2 hrs.) and chronic exposure (2-6 weeks), we found a trend in the increase of lung adenocarcinoma respectively for a total dose of 50 cGy and 75 cGy. Furthermore, when we added neutron exposure to the 75 cGy of GCRsim, we saw a further increase in the incidence of adenocarcinoma. We interpret these findings to suggest that the risks of carcinogenesis are heightened with doses anticipated during a round trip to Mars, and this risk is magnified when coupled with extra neutron exposure that are expected on the Martian surface. We also observed that risks are reduced when the NASA official 33-beam GCR simulations are provided at high dose rates compared to low dose rates.

Short-term predictors of stereotactic radiosurgery outcome for untreated single non-small cell lung cancer brain metastases: a restrospective cohort study.

Stereotactic radiosurgery (SRS) is an option for brain metastases (BM) not eligible for surgical resection, however, predictors of SRS outcomes are poorly known. The aim of this study is to investigate predictors of SRS outcome in patients with BM secondary to non-small cell lung cancer (NSCLC). The secondary objective is to analyze the value of volumetric criteria in identifying BM progression. This retrospective cohort study included patients >18 years of age with a single untreated BM secondary to NSCLC. Demographic, clinical, and radiological data were assessed. The primary outcome was treatment failure, defined as a BM volumetric increase 12 months after SRS. The unidimensional measurement of the BM at follow-up was also assessed. One hundred thirty-five patients were included, with a median BM volume at baseline of 1.1 cm3 (IQR 0.4-2.3). Fifty-two (38.5%) patients had SRS failure at follow-up. Only right BM laterality was associated with SRS failure (p=0.039). Using the volumetric definition of SRS failure, the unidimensional criteria demonstrated a sensibility of 60.78% (46.11%-74.16%), specificity of 89.02% (80.18%-94.86%), positive LR of 5.54 (2.88-10.66) and negative LR of 0.44 (0.31-0.63). SRS demonstrated a 61.5% local control rate 12 months after treatment. Among the potential predictors of treatment outcome analyzed, only the right BM laterality had a significant association with SRS failure. The volumetric criteria were able to identify more subtle signs of BM increase than the unidimensional criteria, which may allow earlier diagnosis of disease progression and use of appropriate therapies.

Trends in work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK: descriptive findings from The Health and Occupation Research (THOR) network 1996-2019.

BACKGROUND: Occupational exposure to metals can be associated with respiratory diseases which can adversely affect the individual's health, finances and employment. Despite this, little is known about the incidence of these respiratory conditions over prolonged periods of time. AIMS: This study aimed to investigate the trends in the incidence of work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK. METHODS: Cases of occupational respiratory diseases caused by nickel, chromium or cobalt reported to Surveillance of Work-related and Occupational Respiratory Disease (SWORD), the UK-based surveillance scheme between 1996 and 2019 (inclusive), were extracted and grouped into six 4-year time periods. Cases were characterised by causative metal exposure, occupational and industrial sector. Incidence rates diseases (adjusted for physician participation and response rate) were calculated using ONS employment data. RESULTS: Of cases reported to SWORD during the study period, 1% (173 actual cases) of respiratory problems were attributed to nickel, chromium or cobalt. Diagnoses of asthma compromised the largest proportion of diagnoses (74.4%), followed by lung cancer (8.9%) and pneumoconiosis (6.7%). Cases had a mean age of 47 years (SD 13); 93% were men. The annual incidence fell from 1.6 per million employed in the first 4-year period, to 0.2 in the most recent period. CONCLUSIONS: Over 24 years, a decline in the incidence of metal-related occupational respiratory diseases was observed in the UK. This could be attributed to improvements in working conditions which resulted in reduced metal exposure but could also be due to closure of industries that might have generated case returns.

A nested case-control study of untargeted plasma metabolomics and lung cancer among never-smoking women within the prospective Shanghai Women's Health Study.

The etiology of lung cancer in never-smokers remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Here, we aimed to enhance our understanding of lung cancer pathogenesis among never-smokers using untargeted metabolomics. This nested case-control study included 395 never-smoking women who developed lung cancer and 395 matched never-smoking cancer-free women from the prospective Shanghai Women's Health Study with 15,353 metabolic features quantified in pre-diagnostic plasma using liquid chromatography high-resolution mass spectrometry. Recognizing that metabolites often correlate and seldom act independently in biological processes, we utilized a weighted correlation network analysis to agnostically construct 28 network modules of correlated metabolites. Using conditional logistic regression models, we assessed the associations for both metabolic network modules and individual metabolic features with lung cancer, accounting for multiple testing using a false discovery rate (FDR) < 0.20. We identified a network module of 121 features inversely associated with all lung cancer (p = .001, FDR = 0.028) and lung adenocarcinoma (p = .002, FDR = 0.056), where lyso-glycerophospholipids played a key role driving these associations. Another module of 440 features was inversely associated with lung adenocarcinoma (p = .014, FDR = 0.196). Individual metabolites within these network modules were enriched in biological pathways linked to oxidative stress, and energy metabolism. These pathways have been implicated in previous metabolomics studies involving populations exposed to known lung cancer risk factors such as traffic-related air pollution and polycyclic aromatic hydrocarbons. Our results suggest that untargeted plasma metabolomics could provide novel insights into the etiology and risk factors of lung cancer among never-smokers.

[Retrospective Study of Bronchoscopic Intervention Therapy for Bronchopleural Fistula Induced by Pulmonary Surgery].

BACKGROUND: As a new technique developed in recent years, bronchoscopic intervention therapy has the advantages of minimal invasion, high safety and repeatability. The aim of this study is to investigate the clinical characteristics of bronchopleural fistula (BPF) induced by surgeries for lung malignancies or benign diseases and the effect of bronchoscopic intervention therapy for BPF, so as to provide support for prevention and treatment of BPF. METHODS: Data 64 patients with BPF who were treated by bronchoscopic intervention in Respiratory Disease Center of Dongzhimen Hospital, Beijing University of Chinese Medicine from June 2020 to September 2023 were collected. Patients with fistula diameter ≤5 mm were underwent submucous injection of macrogol, combined with blocking therapy with N-butyl cyanoacrylate, medical bioprotein glue or silicone prosthesis. Patients with fistula diameter >5 mm were implanted with different stents and cardiac occluders. Locations and characteristics of fistulas were summarized, meanwhile, data including Karnofsky performance status (KPS), shortbreath scale (SS), body temperature, pleural drainage volume and white blood cell count before and after operation were observed. RESULTS: For all 64 patients, 96 anatomic lung resections including pneumonectomy, lobectomy and segmentectomy were executed and 74 fistulas occurred in 65 fistula locations. The proportion of fistula in the right lung (63.5%) was significantly higher than that in the left (36.5%). Besides, the right inferior lobar bronchial fistula was the most common (40.5%). After operation, KPS was significantly increased, while SS, body temperature, pleural drainage volume and white blood cell count were significantly decreased compared to the preoperative values (P<0.05). By telephone follow-up or readmission during 1 month to 38 months after treament, median survival time was 21 months. 33 patients (51.6%) showed complete response, 7 patients (10.9%) showed complete clinical response, 18 patients (28.1%) showed partial response, and 6 patients (9.4%) showed no response. As a whole, the total effective rate of bronchoscopic intervention for BPF was 90.6%. CONCLUSIONS: BPF induced by pulmonary surgery can lead to severe symptoms and it is usually life-threating. Bronchoscopic intervention therapy is one of the fast and effective therapeutic methods for BPF.

Lung fibre burden and risk of malignant mesothelioma in shipyard workers: a necropsy-based case-control study.

OBJECTIVES: In Italy, the highest pleural cancer mortality and incidence have been observed among Italian regions where the 2 largest Italian shipyards were (and are) located. The objective of this study was to assess the exposure-response relationship for mesothelioma among male workers employed in the Monfalcone, Italy, shipyard. METHODS: We conducted a necropsy-based case-control study. Cases (N = 102) were mesothelioma decedents and controls were those with lung cancer (N = 84). Complete job histories were available; the lung fibre content was measured using a scanning electron microscope with X-ray fluorescence, after sample preparation according to the European Respiratory Society guidelines. Odds ratios and 95% confidence intervals of mesothelioma by fibre type and lung fibre burden, as a categorical or continuous variable, were assessed by unconditional logistic regression, adjusted for age and time since exposure cessation. Analyses for the amphibole and chrysotile lung fibre burden were mutually adjusted. We calculated a cumulative exposure index by applying a job-exposure matrix to the job histories of study cases and assessed its correlation with the lung fibre burden. RESULTS: We found an odds ratio of 22.0 (confidence intervals 5.66-85.7) for the highest lung fibre burden category (mean 43.8 million total asbestos fibres per gram of dry tissue) compared with the reference (mean 0.48). Using log10-transformed lung fibre burden, we found that the odds ratio was 3.71 (confidence intervals 2.03-6.79) for a 10-fold lung fibre burden increase. Results for the amphibole lung fibre burden were similar. Odds ratios increased over chrysotile lung fibre burden categories (P-trend = 0.025), and the odds ratio for a 10-fold increase was 4.73 (confidence intervals 0.32-70.4). CONCLUSIONS: The cumulative exposure index was correlated with total and amphibole lung fibre burden, but not with chrysotile lung fibre burden. Mesothelioma risk was proportional to total, amphibole, and chrysotile lung fibre burden in shipyard workers.

Fat intake modifies association between cigarette smoking and lung cancer in a prospective cohort study: A potential explanation for the lung cancer paradox.

BACKGROUND & AIMS: It remains unclear why the association between cigarette smoking and lung cancer was substantially stronger in Western countries than in Asian countries. As experimental studies have revealed that fat intake modulates tobacco carcinogen metabolism and the growth of transplanted or carcinogen-induced lung tumors in mice, the present study sought to investigate whether the association between cigarette smoking and lung cancer was modified by intake of total fat and types of fat (saturated, monounsaturated, and polyunsaturated fats) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. METHODS: During a median follow-up of 8.9 years, 1,425 cases of lung cancer were documented from 100,864 participants eligible for the present analysis. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: After adjustment for established or suspected confounders, the strength of the association between cigarette smoking and lung cancer was remarkably larger among individuals with high fat intake. HRs (95% CIs) comparing current with never smokers were 23.0 (13.4, 39.6), 32.7 (20.3, 52.8), and 59.8 (30.2, 118.2) for the tertile 1 (≤13.48 g/day), tertile 2 (13.49-21.89 g/day), and tertile 3 (≥21.90 g/day) of saturate fat intake, respectively. A similar pattern of the non-significant interaction was observed when the accumulated amount of cigarette smoking (1-19, 20-39, and ≥40 vs. 0 pack-years) was entered into the regression models. CONCLUSIONS: The present study showed that lung cancer risk associated with both the status and accumulated amount of cigarette smoking was remarkably stronger in individuals with high intakes of fat, particularly saturated fat. However, this interaction was not statistically significant and thus warrants further investigations in other studies.

From immune checkpoints to therapies: understanding immune checkpoint regulation and the influence of natural products and traditional medicine on immune checkpoint and immunotherapy in lung cancer.

Lung cancer is a disease of global concern, and immunotherapy has brought lung cancer therapy to a new era. Besides promising effects in the clinical use of immune checkpoint inhibitors, immune-related adverse events (irAEs) and low response rates are problems unsolved. Natural products and traditional medicine with an immune-modulating nature have the property to influence immune checkpoint expression and can improve immunotherapy's effect with relatively low toxicity. This review summarizes currently approved immunotherapy and the current mechanisms known to regulate immune checkpoint expression in lung cancer. It lists natural products and traditional medicine capable of influencing immune checkpoints or synergizing with immunotherapy in lung cancer, exploring both their effects and underlying mechanisms. Future research on immune checkpoint modulation and immunotherapy combination applying natural products and traditional medicine will be based on a deeper understanding of their mechanisms regulating immune checkpoints. Continued exploration of natural products and traditional medicine holds the potential to enhance the efficacy and reduce the adverse reactions of immunotherapy.

Radon exposure risks among residents proximal to gold mine tailings in Gauteng Province, South Africa: a cross-sectional preliminary study protocol.

Gold mine tailings, a legacy of the mining industry, harbors significant amount of radon gas, a classified human carcinogen. Radon exposure, especially near tailings, is a significant public health threat, potentially leading to increased risk of lung cancer, leukemia, and chronic obstructive pulmonary disease (COPD). These health problems are often associated with lower survival rates and significant financial burdens. This ongoing research aim to evaluating the relationship between indoor radon exposure and lung cancer, leukemia, and COPD risks among residents proximal to gold mine tailings in Gauteng Province, South Africa. This cross-sectional preliminary study focus on two distinct groups: Riverlea (exposed group, <2 km to Gold mine tailings) and Orlando East (unexposed group, >2 km to Gold mine tailings). Indoor radon levels is measured using AlphaE monitors, while health risks (lung cancer, leukemia, and COPD) linked to exposure are evaluated through interview-administered questionnaire and secondary data from Gauteng Health Department. Of the 476 residents randomly selected for this study, 300 have already participated, with balanced representation from both the exposed and unexposed groups. The study will compare indoor radon levels and health outcomes between the two groups. This study's results could aid in creating targeted interventions and policies to mitigate indoor radon exposure risks and safeguard vulnerable communities from this significant public health hazard.