Lung Cancer Incidence Research Articles

Machine-Learning Based Prediction of Lung Cancer

The incidence of lung cancer has now exceeded all other types of cancer globally, making it the leading cause of cancer-related deaths. Compared to other types of cancer, lung cancer has a poor prognosis and high mortality rate, making it challenging for humans to accurately predict its incidence rates. The goal of the study is to implement machine learning techniques for the early detection of lung cancer, which can increase patient survival rates. To find the most important factors and predict the possibility of lung cancer, a variety of data mining approaches, including logistic regression, k-means, and apriori algorithms are used in this study. Age, gender, smoking habit, and medical history are a few of the factors included in the dataset used for the study. The logistic regression classifier shows an accuracy of 95% for the classification of lung cancer in patients. The simulation results obtained from the k-means clustering algorithm shows that the main causes for the possible occurrence of lung cancer are chronic diseases, fatigue, allergy, wheezing, alcohol consumption habit, and breath problem. Similarly, according to the association rule's findings, there is no chance of lung cancer developing in a non-drinker who is free of peer pressure, allergies, and wheezing issues.

Harnessing natural product polysaccharides against lung cancer and revisit its novel mechanism

The incidence and mortality of lung cancer are on the rise worldwide. However, the benefit of clinical treatment in lung cancer is limited. Owning to important sources of drug development, natural products have received constant attention around the world. Main ingredient polysaccharides in natural products have been found to have various activities in pharmacological research. In recent years, more and more scientists are looking for the effects and mechanisms of different natural product polysaccharides on lung cancer. In this review, we focus on the following aspects: First, natural product polysaccharides have been discovered to directly suppress the growth of lung cancer cells, which can be effective in limiting tumor progression. Additionally, polysaccharides have been considered to enhance immune function, which can play a pivotal role in fighting lung cancer. Lastly, polysaccharides can improve the efficacy of drugs in lung cancer treatment by regulating the gut microbiota. Overall, the research of natural product polysaccharides in the treatment of lung cancer is a promising area that has the potential to lead to new clinical treatments. With better understanding, natural product polysaccharides have the potential to become important components of future lung cancer treatments.

Greenness and chronic respiratory health issues: a systematic review and meta-analysis.

The number of chronic respiratory disease (CRD) individuals worldwide has been continuously increasing. Numerous studies have shown that greenness can improve chronic respiratory health issues through different mechanisms, with inconsistent evidence. By quantitatively summarizing existing studies, our purpose is to determine the connection between greenness exposure and various chronic respiratory health. We conducted a comprehensive search on PubMed, EMBASE, and Web of Science core databases to identify relevant studies on the correlation between greenness exposure and chronic respiratory health issues. Studies published up to January 2023 were included in the search. The study used the most frequent indicator (normalized difference vegetation index [NDVI]) as the definition of greenness exposure. We finally identified 35 studies for meta-analysis. We calculated pooled effects across studies using a random-effects model and conducted a subgroup analysis by age and buffer zones to discuss the effects on chronic respiratory health issues. This study showed that 0.1 increments in NDVI were significantly related to lower rates of asthma incidence, lung cancer incidence, and chronic obstructive pulmonary disease (COPD) mortality risk; the pooled RRs were 0.92 (95% CI: 0.85-0.98), 0.62 (95% CI: 0.40-0.95), and 0.95 (95% CI: 0.92- 0.99), respectively. For the age subgroup, the higher greenness exposure level was related to the incidence rate of asthma among teenagers aged 13-18years (RR: 0.91; 95% CI: 0.83-0.99). For the buffer subgroup, a positive relationship with greenness exposure and asthma incidence/prevalence at 200-300m and 800- 1000m buffers, as well as the COPD mortality at 800-1000m buffer, the pooled RRs were 0.92 (95% CI: 0.86-0.98), 0.87 (95% CI: 0.81-0.93), and 0.93 (95% CI: 0.88- 0.98), respectively. Evidence of publication bias was not detected in this study. Our study is the first global meta-analysis between greenness and various CRDs to report an inverse association. Further research is needed in order to determine the effect of greenness exposure on different CRDs. Therefore, when planning for green development, more consideration must be given to public health and green management as intervention measures.

Abstract C094: Real-world clinicopathologic characteristics of young Hispanic patients with lung cancer

Abstract BACKGROUND Hispanics are the largest growing minority in the US. Furthermore, lung cancer remains the cancer with the highest mortality among Hispanic patients. Research has suggested that rates of lung cancer among younger patients have been increasing. Despite this, very little is known about Hispanic patients who were diagnosed with lung cancer at a young age. METHODS A total of 135 patients (65 non-Hispanic [NH] and 70 Hispanic) treated at the University of Miami from 2012-2021 with a diagnosis of lung cancer under the age of 45 were included. Demographic and clinicopathologic characteristics were analyzed. RESULTS The median age at diagnosis for Hispanic and non-Hispanic (NH) was 38yrs vs 40yrs, respectively (p=0.09). A total of 59% of Hispanics were female and 56% of all Hispanics had history of tobacco use (p=0.41). Of the NH, 56% were female and 60% endorsed a history of smoking tobacco. The Hispanic patients were 23% Cuban, 3% Puerto Rican, 16% South/Central American, and 58% not specified. The average time to surgery from a positive biopsy was 23 days for Hispanic and 15 days for NH (p=0.44). The average time to chemotherapy initiation was 35 and 41 days for Hispanics vs NH (p=0.39). The most common histology for both groups was adenocarcinoma, accounting for 60% and 53.8% for Hispanics and NH, respectively. Hispanics have higher trends of metastatic disease at diagnosis (63% vs 58% for NH), although rates did not reach statistical significance (p=0.16). Among those with next generation sequencing results, 60.5% of Hispanic patients had an actionable mutation compared to only 50% of NH patients with the presence of an actionable mutation (p=0.37). CONCLUSION To our knowledge, this is the largest cohort of young Hispanics with lung cancer to be described in the U.S. Despite no statistically significant findings, our single institution analysis did reveal some interesting trends. Our data revealed that the majority of patients in both groups were female, which differs from the incidence of lung cancer in the older population of more male predominance. In our sample, a higher percentage of Hispanic patients were diagnosed at advanced stages of lung cancer. Larger prospective studies will be of interest to better understand the disparities that may exist between different ethnicities among younger patients with lung cancer. Citation Format: Aysswarya Manoharan, Kyle Edwards, Blanca Noriega Esquives, Nora El Abbar, Leana Ramos, Nitin Parikh, Samuel Kareff, Estelamari Rodriguez, Coral Olazagasti. Real-world clinicopathologic characteristics of young Hispanic patients with lung cancer [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 C094.

Abstract C063: Frequency and spectrum of KRAS mutations in lung adenocarcinoma from Black/African American and White/European patients

Abstract Lung cancer is the most common cause of cancer death in the United States and a major source of cancer health disparity. Lung cancer incidence and mortality rates are higher in Black/African American (B/AA) men than in men from other racial/ethnic groups. Lung adenocarcinoma, arising in the alveoli or air sacs of the lung, is the most common subtype of lung cancer in all ethnic/racial groups. Genetic driver mutations can differ among racial/ethnic groups, in the identity of the mutated genes, their mutation frequencies, and the spectrum of mutations for each given gene. In addition, the same mutation could have different effects depending on an individual patient’s genetic background, resulting in differential responses to therapies. Therefore, it is important to identify the frequency and spectrum of driver mutations in different population groups. Protooncogenes from the RAS family, KRAS, NRAS, and HRAS, play a crucial role in cell growth regulation, cell proliferation, and survival. KRAS is frequently mutated in numerous cancer types, including lung adenocarcinoma, and has been reported to be the driver gene in ~30% of lung adenocarcinomas from White/European (W/E) patients. Due to the much lower number of lung cancer samples analyzed from B/AA patients, it has been unclear if the KRAS mutational frequency and spectrum in B/AA lung adenocarcinoma patients differs from that in W/E patients. Here we collected available existing data sets with mutational information on KRAS muations in lung adenocarcinoma from B/AA and W/E patients. We obtained data for 1555 B/AA and 13840 White lung adenocarcinoma patients. While B/AA lung adenocarcinoma patients had a lower prevalence of KRAS mutations (27% vs. 35%) than W/E patients, (χ2 p-value= 5.877e-10), KRAS was still the most frequently mutated cancer driver gene in both groups. The most common KRAS mutations in both B/AA and W/E patients were alterations of glycine 12 to cysteine (G12C), valine (G12V), aspartic acid (G12D), and alanine (G12A), as well as glutamine 61 to histidine (Q61H) and glycine 13 to cysteine (G13C). Given that a substantial proportion of lung adenocarcinoma patients carry a mutated KRAS gene, investigating new potential KRAS-targeting therapies remains especially urgent. To this end, we are investigating polyisoprenylated cysteinyl amide inhibitors (PCAIs), a group of potential cancer therapy agents designed to specifically disrupt and suppress hyperactive G-protein signaling, as caused by mutated RAS proteins. We are testing PCAI efficiacy on B/AA and W/E lung adenocarcinoma cell lines carrying various KRAS mutations. Citation Format: Daniel J. Mullen, Pablo E. Puente, Christopher Leon, Diana I. Romero, Kweku Ofosu-Asante, Yong Huang, Nazarius S. Lamango, Ite A. Offringa. Frequency and spectrum of KRAS mutations in lung adenocarcinoma from Black/African American and White/European patients [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 C063.

Patterns in medical surveillance of workers exposed to lung carcinogens

Abstract One of the most common causes of lung cancer is exposure to occupational carcinogens. Free silica, diesel exhaust fumes, dyes, radon and with asbestos at the top of the list, differ by percentage according to the predominant professional activities in each country. The occupational health doctor is directly involved in the surveillance of the exposed worker, during work or post exposure, in the diagnosis and reporting of occupational cancers. Efficient screening followed by reporting and monitoring cases of occupational lung cancer and, last but not least, reintegration into professional activity are important steps in the medical surveillance of the worker exposed to occupational lung carcinogens. Standardised information collected at the level of occupational exposure monitoring systems, separated by carcinogen category and profession, may form the basis of control and prevention plans. Harmonising medical surveillance at European and global level can lead to a decrease in the incidence and mortality of work-related lung cancer.

Abstract C041: Transcriptomic analysis of prostate cancer patients living with HIV

Abstract Background: Higher incidence and mortality rates of liver, lung, anal, and head and neck cancers are typically seen in patients living with human immunodeficiency virus (HIV). However, some previous studies have a decreased risk of prostate cancer in HIV+ patients, particularly in men from sexual minorities, with no clear biological or epidemiological explanation. Methods: To identify the specific transcriptomic changes and genetic pathways associated with HIV infection and prostate cancer emergence, we performed bulk RNA-Seq analysis on 18 prostate cancer samples (9 HIV+ and 9 HIV-). We first used kallisto to measure gene-level expression. We then performed principal component analysis (PCA) to determine if HIV status clearly clustered patients based on their gene expression levels. We subsequently used DESeq2 to perform differentially expressed transcriptomic analysis to identify genes that are associated with HIV and prostate cancer phenotypes. Samples were clustered based on expression levels of the top differentially expressed genes across the HIV+ and HIV- phenotypes. Gene set enrichment analysis was performed on the gene signatures from the two phenotypes. Using an existing single cell RNA-Seq prostate cancer dataset, we deconvoluted the 18 samples with CIBERSORT to approximate the cell type composition. Results: PCA highlighted no major separation between samples based on HIV status. We identified 450 significantly upregulated genes in HIV+ patients, including YAP1, MAT2A, KLF4, and ERF. We identified 409 upregulated genes in HIV- patients, including MICA, AQP2, and KRT6C. Upregulated genes found in HIV+ patients were significantly enriched in multiple immune response pathways, which is consistent with previous sequencing studies focused on HIV status. After cell type composition estimation, we found the samples to be similar in their cell type distributions - stromal and tumor cells were the largest populations, while immune cells were not well represented. Conclusions: We identified transcriptomic differences that need future studies that directly interrogate the biological pathways that affect the incidence of prostate cancer in patients living with HIV. Citation Format: Hanbing Song, Michelle Li, Jon Akutagawa, Franklin Huang. Transcriptomic analysis of prostate cancer patients living with HIV [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 C041.

MiR-429 Liposome Nanoparticles Inhibit Lung Cancer via Targeting of Hippo/YAP in Lung Cancer Mice

The increasing incidence of lung cancer seriously threatens the safety of human life and property. At present, it is difficult for relevant drugs in clinical treatment to accurately identify and act on cancer cells. Therefore, liposome nanoparticles are used to carry related drugs and genes for targeted therapy, which is of great significance. Hippo/YAP signaling is related to the proliferation and apoptosis of cancer cells. Therefore, in this study, the mechanism of lung cancer cells inhibition was further analyzed by constructing miR-429 liposome nanoparticles. miR-429 liposome nanoparticles were prepared and characterized and then injected into experimental group mice after successful modeling and divided into model group, miR-429 lipid nanoparticle group, Hippo/YAP inhibitor (TDI-011536) group, and Hippo/YAP activator (XMU-MP-1) group. Lung cancer cells were taken to construct miR-429 gene silencing and miR-429 gene overexpression groups, followed by analysis of cell proliferation and levels of miR-429, Hippo and YAP. The miR-429 liposome nanoparticles promote the occurrence and development of lung cancer. The miR-429 has a certain inhibitory effect on Hippo/YAP signaling, where it reduces Hippo/YAP signaling activity and inhibits the growth of lung cancer cells. The miR-429 liposome nanoparticles can inhibit Hippo/YAP signaling, reduce their expression, thereby inhibiting lung cancer cell growth and inducing apoptosis, so miR-429 liposome nanoparticles might be used in treating lung cancer.

Abstract C093: Increasing racial diversity of lung adenocarcinoma cell lines to mitigate lung cancer health disparities

Abstract Lung cancer is the leading cause of cancer death in the United States and worldwide, and a significant source of cancer health disparities. Black/African American (B/AA) men exhibit the highest rate of lung cancer death compared to any other racial group. Compared to White men, B/AA men have a 12% higher lung cancer incidence rate and a 15% higher lung cancer death rate. One essential tool in the study of lung cancer is the use of lung cancer cell lines, which can be applied to molecular studies of lung cancer development and progression and pre-clinical drug testing. To minimize disparities in lung cancer research, it is important that cell lines representing different lung cancer histological subtypes, carrying different cancer driver genes, and representing different races and ethnicities be available. This is particularly relevant for lung cancer cell lines from B/AA men. We reviewed the availability of lung cancer cell lines and observed a considerable imbalance in the representation of cell lines from different population groups. We identified over 800 lung cancer cell lines, with the majority of lung cancer cell lines derived from White and Asian patients, and only 31 lung cancer cell lines from B/AA patients. In addition, we did not find any cell lines from Hispanic/Latin(x) (H/L), American Indian/American Native (AI/AN), or Native Hawaiian or other Pacific Islander (NHOPI) patients. Focusing on lung adenocarcinoma, the most common type of lung cancer, we aim to increase the representation of B/AA cell lines by creating new cell lines from B/AA lung cancer patients, as well as by generating isogenic cell line variants from existing lung cancer cell lines, such as NCI-H23. NCI-H23 was derived from a Black male patient with a KRAS G12C heterozygous mutation. We use CRISPR/Cas9-based genome editing to replace the KRAS G12C mutation with other KRAS mutations found in B/AA patients, including KRAS G12V, KRAS G12A, and KRAS G13C. The lack of an appropriately diverse collection of lung cancer cell lines significantly limits racially and ethnically inclusive lung cancer research. This hinders the ability to develop inclusive models, screen comprehensively for therapeutic compounds, and pre-clinically test new drugs. Ultimately, this leads to an under-development of therapies that can increase the survival of minority and underserved patients. The noted lack of cell lines from underrepresented groups should mobilize researchers and clinicians to establish additional cell lines and ensure appropriate representation of all population groups in this critical pre-clinical research resource. Citation Format: Christopher Leon, Matthew Gladstone, Chunli Yan, Diana I. Romero, Yong Huang, Kweku Ofosu-Asante, Nazarius S. Lamango, Ite A. Offringa. Increasing racial diversity of lung adenocarcinoma cell lines to mitigate lung cancer health disparities [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 C093.

Association between brown sugar intake and decreased risk of cancer in the Amami islands region, Japan.

Although excess white sugar intake imposes various health burdens, brown sugar is high in minerals, polyphenols, and polycosanol. However, few epidemiological studies have assessed brown sugar intake for health benefit. People in the Amami islands region, with a relatively high proportion of individuals with longevity, consume brown sugar as a type of refreshment. This cohort study was conducted in Amami to clarify the association of brown sugar intake with mortality risk and cancer incidence. Participants were recruited from the general population of Amami as part of the Japan Multi-Institutional Collaborative Cohort Study. The number of eligible participants was 5004 (2057 men and 2947 women). During the median follow-up period of 13.4 years, 274 deaths and 338 cases of cancer were observed. HRs and 95% CIs were estimated using the Cox proportional hazard model, after adjusting for sugar-related and other variables. After adjusting for their related confounding factors, brown sugar intake was associated with decreased HRs and a decreasing trend for all-site and stomach cancer incidence (p = 0.001 and 0.017, respectively) in women and men, and for breast cancer incidence (p = 0.034) in women. Additionally, a decreasing trend in the HRs for lung cancer incidence was observed among never and ex-smokers (p = 0.039). Decreased HRs for overall death, cancer, and cardiovascular disease were not apparent. Brown sugar intake was associated with decreased risk of all-site, stomach, and breast cancer incidences in the Amami population.

Abstract B117: A trend analysis of cancer incidence in Guam from 2002-2018

Abstract Pacific Islanders are one of the fastest growing population groups in the United States, and serious disparities in health outcomes exist in this group, with cancer being the leading cause of death. In Guam, the five most common cancer sites are lung and bronchus, breast, prostate, colon, and liver. While cancer appears to be less prevalent in Guam overall compared to the US (279.9 vs. 435.0), Micronesians living in Guam exhibit higher rates than the US for lung and bronchus (174.7 vs. 67.7), breast (137.5 vs. 126.8), prostate (143.1 vs. 107.0), and liver (36.2 vs. 7.8) cancer incidence, according to the 2013-2017 Guam Cancer Facts and Figures. The purpose of this study is to discern these changes in trends of cancer incidence for all cancers and the top five cancer sites in Guam. Among the 7,974 malignant cases recorded in the Guam Cancer Registry, the five most prevalent cancer sites, lung and bronchus (N = 1308), breast (N = 1195), prostate (N = 901), colon (N = 562), and liver (N = 364) were observed alongside all cancer sites. Using Guam Public Health’s 2000 population data and 2010 and 2020 Guam Census data points, quadratic regression methods were employed to estimate Guam’s population for each of the other diagnosis years between 1998-2020. Age-adjusted 5-year moving average incidence rates were calculated for all cancer sites, stratified by both sex (Male = 4155, Female = 3815) and by ethnicity (CHamoru = 3751, Filipino = 1911, Micronesian = 598). Similarly, age-adjusted 5-year moving average incidence rates were calculated for the top five cancer sites. Joinpoint regression analysis were utilized to assess the average annual percent change (AAPC) in cancer incidence rates, along with a 95% confidence interval (CI). A significant decrease in all cancer site incidence among males and females was observed from 2005 to 2016 (APC = -2.33, 95% CI: -2.9, -2.1) followed by a non-significant decrease. Among females, colon cancer incidence exhibited the highest significant increase from 2010 to 2018 (APC = 4.0, 95% CI: 2.0, 8.1), whereas lung cancer incidence exhibited the highest significant decrease from 2014 to 2018 (APC = -6.0, 95% CI: -8.5, -3.9). As for males, significant decreases were observed for all cancer sites and prostate cancer incidence from 2005 to 2018 (APC = -3.1, 95% CI: -3.6, -2.8) and 2010-2018 (APC= -5.0, 95% CI: -6.2, -0.7), respectively. Between 2009 to 2019, all cancer-site incidence exhibited increases for all three ethnic groups. Micronesians experienced the largest increase in cancer incidence for all cancer sites (AAPC = 8.1, 95% CI: 7.4, 9.4), as well as for liver cancer (AAPC = 9.8, 95% CI: 7.2, 14.5) and lung cancer (AAPC = 5.5, 95% CI: 4.3, 6.9). This study reveals discernible disparities in cancer incidence over time, particularly when examining variations based on sex and ethnicity. Notably, Micronesians consistently exhibit higher AAPC values, indicating a potentially distinct cancer burden in this particular population. Further research is needed to explore the causes of these epidemiological trends. Citation Format: Cabrini Aguon, Louis Jane Dulana, Rodney Teria, Aurienne Cruz, Su Bin Jin, Grazyna Badowski. A trend analysis of cancer incidence in Guam from 2002-2018 [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 B117.

IL-17A as a new circulating bioindicator for non-small cell lung cancer diagnosis and prognosis.

Lung cancer (LC) is the highest contributor to cancer-associated mortality worldwide. Approximately 85% of all LC incidences involve non-small cell LC (NSCLC). Unfortunately, owing to a significant lack of sensitive and robust bioindicators, most patient diagnoses occur at advanced stages of the disease, thereby resulting in extremely poor patient outcomes. Herein, we elucidated the role of interleukin-17A (IL-17A) among NSCLC patients. Circulating IL-17A content was measured using enzyme-linked immunosorbent assay (ELISA), and its diagnostic and prognostic abilities were assessed using the receiver operating characteristic (ROC) curve and Kaplan-Meier analysis, respectively. Our analysis revealed that circulating IL-17A levels were significantly augmented among NSCLC vs. control samples. Moreover, based on our area under the curve (AUC) analysis, circulating IL-17A levels fared considerably better than the standard bioindicator carcinoembryonic antigen (CEA) in both testing and validation cohorts. Notably, we also revealed that the circulating IL-17A levels were accurately and reliably predicted in early-stage NSCLC patients. Besides, we demonstrated a strong correlation between elevated circulating IL-17A expression and worse prognosis among NSCLC patients. Herein, we demonstrated that circulating IL-17A levels can serve as reliable and potent diagnostic and prognostic bioindicators for NSCLC.

Oxidative stress induction by OCPs and OPPs pesticides may cause lung cancer incidence

Background and aims Pesticides are nowadays known as one of the most important causes of human disorders worldwide. The aim of the present study was to investigate the role of organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in the development of lung cancer. Methods We determined the levels of seven derived OCP residues (α-HCH, β-HCH, γ-HCH, 2,4 DDT, 4,4 DDT, 2,4 DDE, and 4,4 DDE) and enzymatic antioxidant biomarkers including paraoxonase-1 (PON-1), erythrocyte’s acetylcholinesterase (AChE), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and non-enzymatic antioxidant biomarkers, including total antioxidant capacity (TAC), protein carbonyl (PC), malondialdehyde (MDA), and nitric oxide (NO) in the blood samples of 51 lung cancer patients and 51 healthy subjects as controls. Furthermore, the effects of OPP exposure on the development of lung cancer and oxidative stress (OS) are indirectly assessed by measuring AChE and PON-1 enzyme activities. Results The average values of all the measured OCPs were significantly higher in lung cancer patients when compared with healthy control subjects (p < 0.05). AChE, PON-1, GPx, and CAT activity levels, as well as the amounts of PC, MDA, and NO were higher in patients with lung cancer than in the control subjects (p < 0.05), while TAC values were lower in the patients. Moreover, our data showed a significant association between OCP concentrations and OS parameters (p < 0.05). Conclusion The results suggest that OCPs and OPPs may have a role in lung cancer incidence in southeastern Iran, and at least one of the mechanisms by which OCPs and OPPs may contribute to increasing the development of lung cancer in the studied area is through OS generation.

Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study

In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer. The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing. Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis. TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer. Ministry of Health and Welfare of Taiwan.

Contemporary Incidence of Synchronous Multiple Primary Lung Cancers and Survival in the Era of Lung Cancer Screening.

Up to 15% of lung cancer patients have multiple suspicious nodules. While some of these nodules may represent metastatic lung cancer, others represent synchronous multiple primary lung cancer (SMPLC). The incidence of SMPLC ranges from 0.8% to 8.4% and appears to be increasing. Inconsistent identification of SMPLC can be detrimental for patients who are misdiagnosed as having intrapulmonary metastasis and not offered stage-based treatment. We sought to identify the contemporary incidence of SMPLC at a tertiary institution. From January 2018 to September 2019, patients who underwent lung cancer resection were retrospectively reviewed. Patients with SMPLC were identified using the modified Martini-Melamed criteria. During the 21-month period, 227 patients underwent lung cancer resection. There were 47 patients (20.7%) who had 119 pathologically confirmed SMPLC. Most patients had ipsilateral tumors (n = 24, 51.1%) with at least 1 adenocarcinoma (n = 40, 85.1%). Considering histologic subtyping, 38 (80.9%) had histologically distinct tumors. Overall and cancer-specific survival at 4 years was 86% and 90%, respectively. Only patients with 3 or more SMPLC had poor 4-year overall (P = 0.002) and cancer-specific survival (P = 0.043) compared with those with 2 SMPLC. Patient demographics, histology, tumor location, and highest pathologic staging did not affect survival outcomes. Using a strict inclusion criterion, the incidence of SMPLC is higher than previously reported. SMPLC patients have favorable survival outcomes, suggesting that they behave like primary lung cancer, not intrapulmonary metastasis. Awareness of SMPLC by thoracic surgeons is critical in optimizing outcomes in this patient population.

Increased Incidence of Melanoma, Prostate, Lung, Bladder, Renal and Thyroid Cancer after Diagnosis of Primary Cutaneous B-Cell Lymphoma: A SEER Database Analysis

Background: Primary cutaneous B-cell lymphomas (PCBCLs) are a subset of non-Hodgkin lymphomas originating in the skin. The risk of developing other malignancies in PCBCL patients is not known. We evaluated the risk of developing a second primary malignancy after a PCBCL diagnosis. Methods: We utilized the surveillance, epidemiology, and end results (SEER-17) data registry of 9,208,295 patients from 2000-2020 to generate a cohort of 5,435 patients with PCBCL to identify patients at risk for a second primary malignancy. Relative risk was calculated by using the Standardized Incidence Ratio (SIR), defined as the ratio between observed cases (O) and expected cases (E) of malignancies (SIR = O/E). Statistical significance was established based on 95% confidence intervals (CI). Results: Of the 5,435 patients with PCBCL, 847 (16%) received diagnoses of a second malignancy, identifying a higher risk than the general population (SIR, 1.54; 95% CI, 1.43-1.64). Males had a higher chance of developing prostate cancer (SIR, 1.29; 95% CI, 1.07-1.54), melanoma (SIR, 1.49; 95% CI, 1.03-2.09), and bladder cancer (SIR, 1.42; 95% CI, 1.01-1.94). Females were more predisposed to cancers of the lung (SIR, 1.69; 95% CI, 1.25-2.24), thyroid (SIR, 3.06; 95% CI, 1.63-5.23), and kidney (SIR, 2.13; 95% CI 1.06-3.81). For males with PCBCL, there was an increased risk of prostate cancer in patients 60-69 (SIR, 1.53; 95% CI, 1.14-2.02). For females, there was an increased risk of lung cancer in patients over 70, especially in the age group of 70-79 (SIR, 1.84; 95% CI, 1.12-2.84). For cutaneous melanoma, bladder, renal, and thyroid cancer, there was no age group identified to be at a significantly greater risk. Prostate cancer risk was increased within the first year (SIR, 2.09; 95% CI, (1.28 - 3.23) and between 5-10 years after PCBCL diagnosis (SIR, 1.45; 95% CI, 1.04-1.97) .For males, melanoma and bladder cancer were associated with an increased risk between 1-5 years after PCBCL (SIR, 1.91; 95% CI, 1.09-3.11 and SIR, 1.7; 95% CI, 1.01-2.68). Females were at the highest risk of developing thyroid cancer within the first year of PCBCL diagnosis (SIR, 21.11; 95% CI, 10.12-38.83) and lung cancer 1-5 years after PCBCL diagnosis (SIR, 1.7; 95% CI, 1.04-2.62). For renal cancer, there was no latency identified carrying an increased risk. Conclusion: These data, should inform screening strategies for melanoma, prostate, bladder, lung, renal, and thyroid cancer in patients with PCBCL. Males 60-69 within 10 years of PCBCL can benefit from prostate screening. Males within 1-5 years of PCBCL diagnosis can benefit from screening for melanoma and bladder cancer. Females can benefit from thyroid, lung, and renal cancer surveillance. Specifically for females over 70, screening for lung cancer should be considered, and for females within the first year of PCBCL diagnosis, thyroid cancer screening should be considered.

Deciphering exogenous chemical carcinogenicity through interpretable deep learning: A novel approach for evaluating atmospheric pollutant hazards

Cancer remains a significant global health concern, with millions of deaths attributed to it annually. Environmental pollutants play a pivotal role in cancer etiology and contribute to the growing prevalence of this disease. The carcinogenic assessment of these pollutants is crucial for chemical health evaluation and environmental risk assessments. Traditional experimental methods are expensive and time-consuming, prompting the development of alternative approaches such as in silico methods. In this regard, deep learning (DL) has shown potential but lacks optimal performance and interpretability. This study introduces an interpretable DL model called CarcGC for chemical carcinogenicity prediction, utilizing a graph convolutional neural network (GCN) that employs molecular structural graphs as inputs. Compared to existing models, CarcGC demonstrated enhanced performance, with the area under the receiver operating characteristic curve (AUCROC) reaching 0.808 on the test set. Due to air pollution is closely related to the incidence of lung cancers, we applied the CarcGC to predict the potential carcinogenicity of chemicals listed in the United States Environmental Protection Agency's Hazardous Air Pollutants (HAPs) inventory, offering a foundation for environmental carcinogenicity screening. This study highlights the potential of artificially intelligent methods in carcinogenicity prediction and underscores the value of CarcGC interpretability in revealing the structural basis and molecular mechanisms underlying chemical carcinogenicity.

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.

IL-1β mediates the induction of immune checkpoint regulators IDO1 and PD-L1 in lung adenocarcinoma cells

IntroductionInflammation plays a significant role in various cancers, including lung cancer, where the inflammatory cytokine IL-1β is often elevated in the tumor microenvironment. Patients with lung adenocarcinoma show higher levels of serum IL-1β compared to healthy individual. Moreover, IL-1β blockade reduces the incidence and mortality of lung cancer. Our prior studies revealed that alveolar type-II cells, the precursors for lung adenocarcinoma, display an induction in the expression of the enzyme tryptophan 2,3-dioxygenase (TDO2) during normal lung development. This induction of TDO2 coincides with an increase in IL-1β levels and is likely caused by IL-1β. Given that cancer cells can co-opt developmentally regulated pathways, we hypothesized that IL-1β may exert its pro-tumoral function by stimulating TDO2 and indoleamine 2, 3-dioxygenase-1 (IDO1), parallel enzymes involved in the conversion of tryptophan (Trp) into the immune-suppressive oncometabolite kynurenine (Kyn). Our goal was to determine whether IL-1β is a common upstream regulator of immune checkpoint regulators.MethodsTo determine whether IL-1β regulates IDO1, TDO2, PD-L1, and PD-L2, we measured mRNA and protein levels in lung adenocarcinoma cells lines (A549, H1792, H1838, H2347, H2228, HCC364 and HCC827) grown in 2D or 3D and in immortalized normal lung epithelial cells (HBEC3-KT and HSAEC1-KT). To determine the importance of the NFκB pathway in mediating IL-1β -regulated cellular effects, we used siRNA to knockdown RelA/p65 in IL-1β treated cells. The levels of Trp and Kyn in the IL-1β-treated cells and media were measured by mass spectrometry.ResultsUpon IL-1β stimulation, lung adenocarcinoma cells exhibited significant increases in IDO1 mRNA and protein levels, a response that depended on the NFκB pathway. Interestingly, this induction was more pronounced in 3D spheroid cultures compared to monolayer cultures and was not observed in normal immortalized lung epithelial cells. Furthermore, the conversion of Trp to Kyn increased in cells exposed to IL-1β, aligning with the heightened IDO1 expression. Remarkably, IL-1β also upregulated the expression of programmed death ligand-1 (PD-L1) and PD-L2 in multiple cell lines, indicating that IL-1β triggers parallel immune-suppressive mechanisms in lung adenocarcinoma cells.ConclusionsOur studies demonstrate that lung adenocarcinoma cells, but not normal immortalized lung epithelial cells, respond to IL-1β signaling by inducing the expression of parallel immune checkpoint proteins that have the potential to promote immune evasion.AWNWNjEXZEagXxNY6iY8VPVideo

Risk profiles and incidence of cardiovascular events across different cancer types

Cancer survivors are at increased risk for cardiovascular (CV) disease, although additional data are needed to better understand the incidence of CV events across different malignancies. This study sought to characterize the incidence of major adverse CV events [myocardial infarction, stroke, unstable angina (MACE), or heart failure (HF)] across multiple cancer types after cancer diagnosis. Patients were identified from a USA-based administrative claims database who had index cancer diagnoses of breast, lung, prostate, melanoma, myeloma, kidney, colorectal, leukemia, or lymphoma between 2011 and 2019, with continuous enrollment for ≥12 months before diagnosis. Baseline CV risk factors and incidence rates of CV events post-index were identified for each cancer. Multivariable Cox hazards models assessed the cumulative incidence of MACE, accounting for baseline risk factors. Among 839 934 patients across nine cancer types, CV risk factors were prevalent. The cumulative incidence of MACE was highest in lung cancer and myeloma, and lowest in breast cancer, prostate cancer, and melanoma. MACE cumulative incidence for lung cancer was 26% by 4 years (2.7-fold higher relative to breast cancer). The incidence of stroke was especially pronounced in lung cancer, while HF was highest in myeloma and lung cancer. CV events were especially increased following certain cancer diagnoses, even after accounting for baseline risk factors. Understanding the variable patient characteristics and associated CV events across different cancers can help target appropriate CV risk factor modification and develop strategies to minimize adverse CV events and improve patient outcomes.