Risk Of Developing Lung Cancer Research Articles

Lung cancer among patients with secondhand smoke exposure: A systematic review.

e22506 Background: Smoking tobacco is recognized as the leading cause of lung cancer. However, it is imperative to note that 10–15% of lung cancer patients have no history of smoking, and that lung cancer remains the leading cause of cancer deaths among non-smokers. Since passive smokers are exposed to many carcinogenic compounds in the exhaled smoke, it is naturally plausible that secondhand smoking (SHS) is a risk factor for lung cancer. However, current USPSTF screening guidelines for lung cancer with low dose CT (LDCT) do not include patients exposed to SHS. We performed a systematic review to highlight SHS as an etiology of lung cancer and insights for inclusion in cancer screening criteria. Methods: We utilized the PubMed, Medline, Science Direct, and ClinicalTrials.gov databases to search for relevant literature using keywords ('low Dose CT,' 'secondhand smoke,' 'lung cancer'). The search strategy was designed to ensure a comprehensive retrieval of pertinent literature, minimizing the possibility of omitting articles due to insignificant spelling and/or semantic variations. Eligible studies had to be published between 2010 and 2023 and focused on examining the effect of SHS in populations at risk of lung cancer or those undergoing lung cancer screening. Articles not available in English were excluded from this systematic review. In total, 239 relevant articles were retrieved from all databases, narrowing down to 14 articles after the initial screening and further reducing to 4 articles after the second round of screening. Results: Three of the four articles included in our systemic review were conducted in Asia. A study by He et al. showed a substantial increase in the relative risk of lung cancer among SHS (RR 2.00; 95% CI, 0.62-6.40), with significant dose-response relationships between cumulative SHS exposure at home and work and the increased risk of cause-specific and total mortality. Another observational study on the use of LDCT in Japan has interestingly shown a shifting landscape of lung cancer demographics, with 49.6% of patients identified as never-smokers and 70.0% of the never-smoker lung cancer patients having SHS exposure. Secondhand smoking has also been reported to increase the risk of pulmonary nodules (HR 1.17; 95% CI, 1.01-1.35) and pulmonary emphysema (OR 13.6; 95% CI, 1.70-106.1) in those with moderate-to-high SHS exposure, which was the population where lung cancer was more prevalent. Conclusions: Our findings suggest a critical gap in current healthcare recommendations, specifically addressing the absence of guidelines for LDCT screening in individuals with moderate-to-high SHS exposure despite established evidence linking SHS to a significant increase in the risk of lung cancer development. More studies are needed to formulate evidence-based guidelines for lung cancer screening and detection in this population, given the expected mortality reduction benefit.

Impact of smoking reduction on lung cancer risk in patients with COPD who smoked fewer than 30 pack-years: a nationwide population-based cohort study

BackgroundThe effects of smoking reduction on the incidence of lung cancer in patients with chronic obstructive pulmonary disease (COPD) are not well known. This study aimed to investigate the effects of changes in smoking habits after COPD diagnosis on lung cancer development in patients who smoked less than 30 pack-years.MethodsThis nationwide retrospective cohort study included 16,832 patients with COPD who smoked less than 30 pack-years at the time of COPD diagnosis. Based on changes in smoking habits in the health screening examination data, smokers were categorized into three groups: quitters, reducers, and sustainers. The primary outcome was the risk of lung cancer development, which was estimated using the Cox proportional hazards model. We also modelled the amount of smoking reduction as a continuous variable.ResultsDuring a median follow-up of 4 years, the cumulative incidence of lung cancer was the highest among sustainers, followed by reducers and quitters. Compared with sustainers, reducers (adjusted HR 0.74, 95% CI:0.56–0.98) and quitters (adjusted HR 0.78, 95% CI:0.64–0.96) had a significantly lower risk of lung cancer. Incidence of lung cancer showed a decreasing trend with a decreasing amount of smoking (P for linearity < 0.01).ConclusionsIn patients with COPD who smoked less than 30 pack-years, smoking reduction and cessation lowered the risk of lung cancer.

Association between high levels of nitrogen dioxide and increased cumulative incidence of lung cancer in patients with idiopathic pulmonary fibrosis.

Lung cancer is a fatal complication of idiopathic pulmonary fibrosis (IPF) with a poor prognosis. However, the association between individual exposure to air pollutants and lung cancer development in patients with IPF is unknown. This study aimed to assess the effect of individual exposure to nitrogen dioxide (NO2) on lung cancer development in patients with IPF. We enrolled 1085 patients from an IPF cohort in the Republic of Korea (mean age 65.6 years, males 80.6%). We estimated individual-level long-term exposures to NO2 at the patients' residential addresses using a national-scale exposure prediction model based on data from air quality regulatory monitoring stations. To evaluate the association between NO2 levels and lung cancer development in IPF, we used an individual- and area-level covariates adjusted model as our primary model. The estimated average annual NO2 concentration was 23.1 ppb. During a median follow-up of 4.3 years, 86 patients (7.9%) developed lung cancer. NO2 concentration was associated with lung cancer development in an unadjusted model (HR 1.219; p=0.042), while a marginal association was found in the primary model (HR 1.280; p=0.084). When NO2 concentration was stratified by the median value (21.0 ppb), exposure to high NO2 levels (≥21.0 ppb) was associated with a 2.0-fold increase in the risk of lung cancer development (HR 2.023; p=0.047) in the primary model. Individual exposure to high NO2 levels may increase the risk of lung cancer development in patients with IPF.

Heritable Traits and Lung Cancer Risk: A Two-Sample Mendelian Randomization Study.

Lung cancer is a complex polygenic disorder. Analysis with Mendelian randomization (MR) allows for genetically predicted risks to be estimated between exposures and outcomes. We analyzed 345 heritable traits from the United Kingdom Biobank and estimated their associated effects on lung cancer outcomes using two sample MR. In addition to estimating effects with overall lung cancer, adenocarcinoma, small cell lung cancer, and squamous cell lung cancers, we performed conditional effect modeling with multivariate MR (MVMR) and the traits of alcohol use, smoking initiation, average pre-tax income, and educational attainment. Univariate MR provided evidence for increased age at first sexual intercourse (OR, 0.55; P = 6.15×10-13), educational attainment (OR, 0.24; P = 1.07×10-19), average household income (OR, 0.58; P = 7.85×10-05), and alcohol usually taken with meals (OR, 0.19; P = 1.06×10-06) associating with decreased odds of overall lung cancer development. In contrast, a lack of additional educational attainment (OR, 8.00; P = 3.48×10-12), body mass index (OR, 1.28; P = 9.00×10-08), pack years smoking as a proportion of life span (OR, 9.93; P = 7.96×10-12), and weekly beer intake (OR, 3.48; P = 4.08×10-07) were associated with an increased risk of overall lung cancer development. Many heritable traits associated with an increased or inverse risk of lung cancer development. Effects vary based on histologic subtype and conditional third trait exposures. We identified several heritable traits and presented their genetically predictable impact on lung cancer development, providing valuable insights for consideration.

The association between hormone therapy and the risk of lung cancer in postmenopausal women: a 16-year nationwide population-based study.

Although an association between hormone therapy (HT) and the risk of developing lung cancer has been reported, the results on the topic are inconsistent. Our study objective was to investigate whether postmenopausal women who undergo HT exhibit a risk of developing lung cancer. In this matched cohort study, we obtained the data of 38,104 postmenopausal women older than 45 years who were treated using HT between 2000 and 2015 from Taiwan's National Health Insurance Research Database, and 152,416 matched participants who were not treated using HT were enrolled as controls at a 1:4 ratio. We used a Cox proportional hazards regression model to identify the risk of developing lung cancer during 16 years of follow-up, and the results indicate no significant difference in the proportion of postmenopausal women treated using HT ( P = 0.129) who developed lung cancer and that of those not treated using HT (0.866% [330 of 38,104] vs 0.950% [1,449 of 152,416]). After adjustment for age and other variables, the adjusted hazard ratio was 0.886 (95% CI, 0.666-1.305, P = 0.433), indicating no association between HT and lung cancer development in postmenopausal women. In a subgroup analysis, the risk of lung cancer was significantly lower in the women who were treated using HT when the HT cumulative dosage was ≥401 mg or when the therapy duration was ≥5 years compared with in those not treated using HT; the adjusted hazard ratios were 0.633 (95% CI, 0.475-0.930; P < 0.001) and 0.532 (95% CI, 0.330-0.934; P < 0.001), respectively, after adjustment. Our results indicate that HT is not associated with the risk of lung cancer development in postmenopausal women; furthermore, a higher cumulative dosage and the long-term effects of HT reduce the risk of developing lung cancer.

Air pollution and lung cancer-A new era.

Air pollution and lung cancer-A new era.

Association of MLH1-93G>A polymorphisms toward lung cancer susceptibility and its association with clinical outcome in North Indian patients treated with platinum-based chemotherapy.

Lung cancer is one of the most prevalent and main causes of malignancy-related deaths worldwide, especially in developed countries. Epidemiological studies have demonstrated that individuals having alterations in a particular gene may have a high risk of developing certain types of cancer. In the present study, 500 Indian lung cancer patients and 500 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism method was used to identify the genotype of enrolled individuals and MedCalc statistical package was used for carrying out statistical analysis. In this study, we found a reduced risk of developing adenocarcinoma in patients harboring variant (P = 0.0007) and combined type genotype (P = 0.008), whereas an increased risk for small-cell lung carcinoma (SCLC) development for those subject harboring GA genotypes (P = 0.03) was also observed. Further, heterozygous type and combined type genotype of heavy smokers for MLH1 polymorphism reported a 2-fold (P = 0.001) and 1.8-fold increased risk toward lung cancer development, respectively (P = 0.007). In case of females, the subjects harboring a variant allele have a significantly reduced risk for lung cancer development (P = 0.0001). For MLH1 polymorphism, reduced risk of developing tumor to T3 or T4 stage was observed (P = 0.04). Moreover, this is the first study reporting overall survival (OS) association for north Indian lung cancer patients with platinum-based doublet chemotherapy; for docetaxel, a three-fold increase in hazard ratio and corresponding low median standard survival time (8.4 months) for mutant and combined type genotype (P = 0.04) was observed. These results suggest that MLH1-93G>A polymorphism is involved in modulating the risk toward lung cancer. Our study also concluded a negative association of OS in patients undergoing carboplatin/cisplatin and docetaxel chemotherapy.

Lung cancer risk in workers occupationally exposed to polycyclic aromatic hydrocarbons with emphasis on the role of DNA repair gene

ObjectiveWorkers in secondary aluminum production plants are occupationally exposed to polycyclic aromatic hydrocarbons (PAHs). We aimed to monitor the concentrations of PAHs in air and in serum of workers at two secondary aluminum production plants. We also investigated the potential risk of lung cancer development among PAHs exposed workers with emphasis on the role of A1AT mutation and APEX1 gene polymorphisms.MethodsThis study included 177 workers from administrative departments and production lines. Blood samples were obtained for estimation of benzo(a)pyrene diol epoxide albumin adduct (BPDE-Alb adduct), anti-Cyclin-B1 marker (CCNB1) and squamous cell carcinoma antigen (SCCAg). Genes’ polymorphism for human apurinic/apyrimidinic endonuclease (APEX1) and alpha-1-anti-trypsin (A1AT) gene mutation were detected.ResultsThere was a significant increase in the level of BPDE-Alb adduct among exposed workers in comparison to non-exposed group. Moreover, 41.67% of exposed workers in El Tebbin had BPDE-Alb adduct level ≥ 15 ng/ml versus 29.6% of workers in Helwan factory. There was a significant increase in tumor markers (SCCAg and CCNB1) among workers whose BPDE-Alb adduct ≥ 15 ng/ml. There was a significant increase in the level of BPDE-Alb adducts in exposed workers carrying homozygous APEX1 genotype Glu/Glu. Furthermore, exposed workers with the Glu/Glu genotype had high tumor markers levels. There was a significant increase in levels of BPDE-Alb adducts in workers carrying A1AT mutant allele. Moreover, workers with mutant A1AT genotype had significantly high tumor markers (SCCAg and CCNB1) levels.ConclusionTherefore, we conclude that aluminum workers may be at a potential risk of lung cancer development due to PAHs exposure. Although PAHs concentrations in air were within the permissible limits, yet evidence of DNA damage was present as expressed by high BPDE-albumin adduct level in exposed workers. Also, elevation of tumor markers (SCCAg and CCNB1) in exposed workers points to the importance of periodic biological monitoring of such workers to protect them from cancer risk.

Association between use of antacid medications (proton pump inhibitors and histamine-2 receptor antagonists) and the incidence of lung cancer: A population-based cohort analysis.

This study investigated the association between antacid administration and lung cancer incidence in a real-world setting. This was a nationwide, retrospective cohort study. The cohort comprised random samples (n = 1,031,392) from the entire South Korean population in 2002. The duration of antacid administration between January 2006 and December 2010 was recorded for each participant. Newly developed lung cancers were counted during the 5-year observation period (January 1, 2006 to December 31, 2010). A total of 437,370 participants aged ≥ 40 years were included, of whom 301,201 (68.9%) had antacid exposure before the diagnosis of lung cancer. A total of 1230 (0.28%) antacid-exposed patients developed lung cancer. Among patients with no antacid exposure or underexposure (n = 136,171), 597 (0.44%) developed lung cancer. In the multivariable analysis, antacid exposure before the diagnosis of lung cancer was independently associated with a reduced incidence of lung cancer (hazard ratio: 0.64; 95% confidence interval: 0.55-0.74; P < .001). Antacid use might be independently associated with a decreased risk of lung cancer development in this cohort study.

Association of the Manganese Superoxide Dismutase (Mn-SOD) Gene C47T Polymorphism with Lung Cancer: A Case-Control Study.

The objective of this study was to determine the association between manganese superoxide dismutase (Mn-SOD) gene C47 T polymorphism and the risk of malignant lung cancer in Iraqi smokers. Blood samples were obtained from 260 lung cancer patients (88 females and 172 males) and 295 healthy individuals (91 females and 204 males). DNA was extracted from blood samples and the SOD2 gene was amplified using specific primers. The nucleotide sequences of the SOD2 gene were analyzed by using BLAST server at National Center for Biotechnology Information (NCBI) and the Raptorx app. TT, CT, and CC genotypes concentrations were 48.1%, 33.2%, and 18.7%, respectively, in the control group. The concentrations of TT, CT, and CC genotypes were 43.5%, 31.5%, and 25%, respectively, in the case group. There were no statistical differences between cases and controls in terms of genotype frequency of SOD2C47T polymorphism. We observed that SOD2C47T polymorphism CT genotype did not increase the risk of lung cancer development compared to those with TT genotype (OR= 0.951, 95% CI = 0.648-1.396; P = 0.798). In addition, it was observed that CC genotype did not increase the risk of lung cancer development in comparison with TT genotype ( OR=0.673, 95% Cl=0.435-1.041: P=0.075). These results indicated that there was no association between SOD2C47T polymorphism and the risk of lung cancer development in Iraqi smokers.

Abstract 3158: Defining the mechanisms that lead to mutational heterogeneity in the normal respiratory epithelium

Abstract It is well established that tobacco smoking causes lung cancer and this is thought to be the result of a progressive accumulation of genomic mutations induced by tobacco smoke exposure; however, until recently a detailed understanding of the effects of smoke exposure on the genomes of cells in the normal bronchial epithelium was lacking. To address this, we defined the genomic architecture of normal airway basal cells in children and non-smoking, smoking and ex-smoking adults. We discovered two populations of basal cells in individuals with a smoking history: those with high mutational burden, driver gene mutations and tobacco-associated mutational signatures, and those with low mutational burden, similar to basal cells from never smokers and with an absence of mutational signatures associated with tobacco exposure. These cells expand preferentially in ex-smokers, accounting for 20-40% of basal cells compared with 2-5% in current smokers. We hypothesise that these cells are cancer-protective and their expansion reduces the risk of lung cancer development after smoking cessation. Understanding the functional differences between high- and low-mutant airway basal cells and the mechanisms by which some cells resist the accumulation of smoking-induced mutations will be crucial to understanding the earliest stages of lung carcinogenesis. To address this, we performed RNAseq on a subset of whole-genome sequenced airway basal cells. Preliminary data show that expression of markers of stemness is significantly different between high- and low-mutant basal cells. In addition, initial analysis shows that pathways such as carcinogen metabolism and MHC class I antigen presentation are higher in high-mutant basal cells. Further analysis in more patients is ongoing. To complement these data, we expanded whole-genome sequenced basal cell clones in culture and performed a range of assays to assess their progenitor and differentiation capacity. We assessed proliferation, colony-forming efficiency, longevity and differentiation and found no apparent differences between low- and high-mutant basal cells. Initial analysis suggests that carcinogen metabolism and MHC class I antigen presentation may be key pathways in establishing heterogeneity in mutational burden and clonal dynamics in the normal airway epithelium. Additional assays and analysis are ongoing and will be the focus of future research. Citation Format: Kate H. Gowers, Sarah E. Clarke, Ayu Hutami Syaraf, Kenichi Yoshida, Moritz J. Przybilla, Hugh Selway, Adam Pennycuick, Peter J. Campbell, Sam M. Janes. Defining the mechanisms that lead to mutational heterogeneity in the normal respiratory epithelium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3158.

Phenotypic and endotypic features of COPD associated with lung cancer development.

e13563 Background: Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease with multiple phenotypes and endotypes and associated with lung cancer development. In this study, we analyzed the clinical features of COPD including various phenotypic and endotypic features from the electronic health records (EHR) as the potential risk factors for lung cancer development in a large cohort of COPD patients. Methods: We identified a COPD cohort based on electronic Medical Records and Genomics (eMERGE) network COPD cohort identification algorithms with minor modifications from the Mount Sinai Data Warehouse (2000-2020) and followed the patients on the first diagnosis of lung cancer. The development of lung cancer in COPD patients was confirmed by manual chart review. We retrieved the clinical features from EHRs and conducted Kaplan Meier (KM) analysis and multivariable Cox-regression modeling for hazard ratio (HR) analysis. Results: We found that 3.8 % of COPD patients (824 out of 21,658) developed lung cancer. While COPD patients with emphysema and smoking history (former or current) showed an increased risk of lung cancer onset, patients with concurrent asthma and corticosteroid (ICS) inhalation history showed a reduced risk of lung cancer onset (adjusted HR in Table). Interestingly, COPD patients with higher eosinophil counts showed late onset of lung cancer (&gt;300 cells/ul, cancer rate at 5y=2.4%, p=&lt; 0.002; 150-300 cells/ul, cancer rate at 5y=2.9%, p=0.003) when compared to patients with low eosinophils count (&lt;150 cells/ul, cancer rate at 5y=3.4%) in a KM analysis. A multivariable analysis adjusted for age, gender, race, smoking status, COPD sub-phenotypes, severe exacerbation history, and ICS inhalation history showed a significantly lower risk of lung cancer in COPD patients with higher eosinophils count (150-300 cells/ul; HR: 0.82, 95% CI: 0.69-0.97, p=0.021 and &gt;300 cells/ul; HR:0.72, 95% CI: 0.57-0.89, p=0.003) when compared to those with low eosinophils count (&lt;150 cells/ul). Conclusions: Our study shows that many phenotypic and endotypic features of COPD are differentially associated with lung cancer development. High eosinophil levels, ICS usage, and concurrent asthma in COPD patients may reduce the risk of lung cancer development. [Table: see text]

Joint Effects of Cigarette Smoking and Green Tea Consumption with miR-29b and DNMT3B mRNA Expression in the Development of Lung Cancer.

In tumor development, increased expression of DNA methyltransferase (DNMT) has been observed. In particular, cigarette smoke and tea polyphenols may influence DNMT3B mRNA expression by regulating microRNA (miR)-29b expression. Herein, we designed a case–control study to evaluate the joint effects of smoking and green tea consumption, with miR-29b and DNMT3B mRNA expression, in lung cancer development. A total of 132 lung cancer patients and 132 healthy controls were recruited to measure miR-29b and DNMT3B mRNA expression in whole blood. Results revealed that lung cancer patients had lower miR-29b expression (57.2 vs. 81.6; p = 0.02) and higher DNMT3B mRNA expression (37.2 vs. 25.8; p < 0.001) than healthy controls. Compared to non-smokers with both higher miR-29b and lower DNMT3B mRNA expression, smokers with both low miR-29b and higher DNMT3B mRNA expression had an elevated risk of lung cancer development (OR 5.12, 95% CI 2.64–9.91). Interactions of smoking with miR-29b or DNMT3B mRNA expression in lung cancer were significant. Interaction of green tea consumption with miR-29b expression and DNMT3B mRNA expression in lung cancer was also significant. Our study suggests that smokers and green tea nondrinkers with lower miR-29b expression and higher DNMT3B mRNA expression are more susceptible to lung cancer development.

Association between Serum Lycopene and Lung Cancer Mortality: An 18-Year Follow-up Study of a National Cohort.

Background: Lycopene is a carotenoid found in some fruits and vegetables that is responsible for the red pigment in tomatoes and tomato products. While many studies have shown a link between lycopene and protection against the initiation and/or progression of lung cancer, data on its effect on lung cancer survivability is limited. Objective: The primary objective of this study was to see if there was a link between lycopene levels in the blood and lung cancer mortality. A secondary goal was to see if dietary factors influence lycopene levels in the blood. Materials and Methods: A retrospective cohort study of 14,358 adults who took part in Phase II of the National Health and Nutrition Examination Survey III was carried out (1991-1994). This dataset served as the baseline for a 15-year (1991-2006) follow-up study, which was correlated with the National Death Index database. The Cox Proportional Hazards Regression Model was used to calculate the HR for all-cause and cancer-related deaths for individuals with high, moderate, and low serum lycopene levels. Results: The unadjusted hazard ratio (HR) of deaths associated with low serum lycopene levels (25 percent cutoff) was 1.67 (95 percent CI=1.24-2.23) and 1.00, respectively (ref). After controlling for multiple risk factors such as age and gender, the HR for lung cancer fatalities was 1.45 (95% CI=1.08-1.96) for low serum levels (25 percent cutoff) with a reference value of 1.00. For low vs. high serum lycopene levels, the adjusted HR for lung cancer death using 3-level categorization (and adjusted for fruits and vegetables) was 1.67 (95 percent CI=1.03-2.71). In addition, the adjusted HR for lung cancer death using 3-level categorization (and unadjusted for fruits and vegetables) was 1.68 (95 percent CI=1.04-2.72) for low serum lycopene levels vs. high serum lycopene levels. Conclusions: The results suggest that high serum lycopene levels may reduce the risk of dying from lung cancer. Furthermore, lycopene may not only reduce the risk of lung cancer development but may also improve survival among lung cancer patients. More research is needed to understand the physiological mechanisms underlying this association. Keywords Serum lycopene, Lung cancer, Mortality risk, Cohort study

Rapid FEV1 Decline and Lung Cancer Incidence in South Korea

Impaired lung function is associated with a higher risk of developing lung cancer. However, lung function is a dynamic variable and must be evaluated longitudinally. This study reports on the relationship between accelerated lung function decline and development of lung cancer. Is accelerated lung function decline associated with the development of lung cancer? A longitudinal, observational study was performed by using epidemiologic data from two population-based studies comprising subjects assessed biannually from 2001 to 2019 in South Korea. Eligible subjects were between 40 and 69 years of age and were followed up by using spirometry. Spirometry measurements were made at each follow-up. Patients with a decline in FEV1 > 60mL per year were defined as rapid FEV1 decliners. The relationship between lung cancer and rapid FEV1 decline was evaluated by using adjusted Cox regression models with covariates, including age, sex, smoking history, FEV1/FVC, and WBC count. Among the 8,549 eligible subjects, 1,287 (15.1%) had rapid FEV1 decline, and 48 (0.6%) had newly developed lung cancer. The risk of lung cancer development was increased in the subjects aged≥ 45 years and those with≥ 30 pack-years of smoking, low baseline FEV1/FVC, low forced expiratory flow between 25%and 75%of vital capacity, rapid FEV1 decline, and increased WBC count. Rapid FEV1 decline was an independent risk factor for lung cancer development (adjusted hazard ratio, 2.34; 95%CI, 1.28-4.28; P= .006). Time-dependent net reclassification improvement showed a benefit of FEV1 decline rate in determining subjects at risk of lung cancer when added to conventional practice (categorical, 0.32 [95%CI, 0.00-0.64]; continuous, 0.83 [95%CI, 0.14-1.25]). The FEV1 decline rate may be a potential biomarker for lung cancer development. Further study is needed to identify whether patients with rapid FEV1 decline warrant lung cancer assessment or screening.

Polymorphisms in DNA Repair and Xenobiotic Biotransformation Enzyme Genes and Lung Cancer Risk in Coal Mine Workers.

Background: Currently coal mining employs over 7 million miners globally. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons and radioactive radon, significantly increasing the risk of lung cancer (LC). The susceptibility for LC is modified by genetic variations in xenobiotic detoxification and DNA repair capacity. The aim of this study was to investigate the association between GSTM1 (deletion), APEX1 (rs1130409), XPD (rs13181) and NBS1 (rs1805794) gene polymorphisms and LC risk in patients who worked in coal mines. Methods: The study included 639 residents of the coal region of Western Siberia (Kemerovo region, Russia): 395 underground miners and 244 healthy men who do not work in industrial enterprises. Genotyping was performed using real-time and allele-specific PCR. Results: The results show that polymorphisms of APEX1 (recessive model: ORadj = 1.87; CI 95%: 1.01–3.48) and XPD (log additive model: ORadj = 2.25; CI 95%: 1.59–3.19) genes were associated with increased LC risk. GSTM1 large deletion l was linked with decreased risk of LC formation (ORadj = 0.59, CI 95%: 0.36–0.98). The multifactor dimensionality reduction method for 3-loci model of gene–gene interactions showed that the GSTM1 (large deletion)—APEX1 (rs1130409)—XPD (rs13181) model was related with a risk of LC development. Conclusions: The results of this study highlight an association between gene polymorphism combinations and LC risks in coal mine workers.

A Nested Case-Control Study of Lung Cancer for Immune Biomarkers

<h3>Purpose/Objective(s)</h3> Smoking is the leading cause of lung cancer, which is the leading cause of cancer mortality worldwide, with 1.2 million deaths a year. Lung cancer has a very poor prognosis; over half of people diagnosed die within one year of diagnosis and the 5-year survival is less than 18%. Prior to cancer development, smokers develop multiple lung problems associated with chronic inflammation, which can promote progression to cancer. The aim of the study was to examine if immune competence would enhance or reduce the risk of lung cancer development among high-risk smokers. The hypothesis is that smokers who developed lung cancer would have a higher frequency of chronic inflammation induced myeloid-derived suppressor cells (MDSC) and/or regulatory T cells (Treg), three years or more prior to lung cancer diagnosis (baseline), compared to smokers who remained cancer-free. Additionally, smokers who developed cancer would have higher levels of certain inflammatory cytokines at baseline. <h3>Materials/Methods</h3> A case-control study of incident lung cancer was conducted within the participants of the Pittsburgh Lung Screening Study (PLuSS), a longitudinal low-dose CT screening study for early detection of lung cancer among smokers with a history of heavy smoking (median 47 pack-years of cigarette smoking). Cases consisted of 40 current or former smokers who developed lung cancer during follow-up after repeated blood draws and the control group consisted of 40 PLuSS participants, free of cancer, who were individually matched to the index case by age, sex, smoking status, and year of blood draw. Live peripheral blood mononuclear cells (PBMC) were thawed and analyzed for MDSC, CD4 T cells, and Treg by flow cytometry. Cytokines and chemokines were quantified in two repeated serum samples per subject using the next generation multiplex immunoassays. <h3>Results</h3> There was no statistically significant difference in overall MDSC percentage of PBMC nor in subtypes (PMN-MDSC, M-MDSC and e-MDSC) between cases and controls. There was also no difference found for Tregs. However, CD4 T cells were elevated in lung cancer cases and were associated with an increased risk of lung cancer overall (odds ratio [OR] = 2.61, 95% confidence interval [CI] = 0.73-9.32, p trend = 0.1409). Lung cancer cases had significantly higher levels of serum inflammatory cytokines IL-17A and Il-12/IL-23p40 at both early (median 84 months) and late time points (7 months prior to cancer diagnosis) (all <i>P</i>s < 0.05). <h3>Conclusion</h3> Lung cancer cases are associated with elevated levels of CD4 T cells and pro-inflammatory cytokines, specifically IL-17A and IL-12/IL-23p40, as early as 7 years before cancer diagnosis. The study has the potential to identify immune cells and soluble factors that mediate lung cancer development in smokers and could be used as early biomarkers for risk assessment or early diagnosis of lung cancer.

Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown aetiology, with a median survival of 2–4 years from the time of diagnosis. Although IPF has unknown aetiology by definition, there have been identified several risks factors increasing the probability of the onset and progression of the disease in IPF patients such as cigarette smoking and environmental risk factors associated with domestic and occupational exposure. Among them, cigarette smoking together with concomitant emphysema might predispose IPF patients to lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer development. To this purpose, IPF and LC share several cellular and molecular processes driving the progression of both pathologies such as fibroblast transition proliferation and activation, endoplasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose IPF patients to LC development. Nintedanib, a tyrosine–kinase inhibitor, was firstly developed as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target molecular pathway. In this review our aim is to describe the updated studies on common cellular and molecular mechanisms between IPF and lung cancer, knowledge of which might help to find novel therapeutic targets for this disease combination.

P60.02 Polymorphisms of APE1(T444G), hOGG1(C977G), XRCC1(G839A), XPD(T2251G), XPG(G3310C), XPC(A2815C) Genes in Lung Cancer Patients

Lung cancer (LC) the leading cause of cancer deaths in males for decades, has recently become one of commonest causes for women too. The DNA repair system is the first barrier in the onset pathway of genomic instability and carcinogenesis under the effect of mutagens. As has been shown in some studies, genetic polymorphisms of the DNA repair system are associated with the risk of LC development (Cai et al.,2014; Liu et al., 2017; Zhou et al.,2015).

Pulmonary Tuberculosis and the Incidence of Lung Cancer among Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Although a history of pulmonary tuberculosis (PTB) is a risk factor for developing both chronic obstructive pulmonary disease (COPD) and lung cancer, it remains unclear whether a history of PTB affects lung cancer development in patients with COPD. Objectives: To investigate whether a history of PTB is associated with an increased risk of lung cancer development in a population with COPD. Methods: This cohort study included a nationwide representative sample of 13,165 Korean men and women with COPD, aged between 50 and 84 years. In addition, to assess whether the relationship between PTB and lung cancer risk differs between participants with and without COPD, a matchedcohort without COPD was included. Participants werematched 1:3 for age, sex, smoking history, and PTB status based on the index health screening examination of corresponding participantswith COPD. The two cohorts were followed up for 13 years (January 1, 2003, to December 31, 2015). PTB was diagnosed on the basis of the results of chest radiography, and incident lung cancer was identified from hospitalization and outpatient visit claims (International Classification of Diseases, Tenth Revision diagnosis code C33 or C34). Results: During 370,617 person-years (PY) of follow-up (median follow-up, 7.7 yr) in the COPD group, we observed 430 incident cases of lung cancer in participants without a history of PTB (incidence rate, 524 per 100,000 PY) and 148 cases in those with a history of PTB (incidence rate, 931 per 100,000 PY). Compared with participants without a PTB history, the fully adjusted subdistribution hazard ratio (95% confidence interval [CI]) for lung cancer in those with a history of PTB was 1.24 (1.03-1.50). The association of PTB history and lung cancer development was more evident in never-smokers with COPD. In contrast, among participants without COPD, the corresponding hazard ratio (95% CI) was 0.98 (0.78-1.22). There was no interaction among PTB, smoking status, and COPD. Conclusions: A history of PTB was associated with an increased risk of developing lung cancer among patients with COPD in our country with an intermediate tuberculosis burden. Patients with COPD with a history of PTB, particularly never-smokers, might benefit from periodic screening or assessment for lung cancer development.