Odds Ratio For Lung Cancer Research Articles

Genomic Insights for Personalized Care: Motivating At-Risk Individuals Toward Evidence-Based Health Practices.

Lung cancer and tobacco use pose significant global health challenges, necessitating a comprehensive translational roadmap for improved prevention strategies. Polygenic risk scores (PRSs) are powerful tools for patient risk stratification but have not yet been widely used in primary care for lung cancer, particularly in diverse patient populations. We propose the GREAT care paradigm, which employs PRSs to stratify disease risk and personalize interventions. We developed PRSs using large-scale multi-ancestry genome-wide association studies and standardized PRS distributions across all ancestries. We applied our PRSs to 796 individuals from the GISC Trial, 350,154 from UK Biobank (UKBB), and 210,826 from All of Us Research Program (AoU), totaling 561,776 individuals of diverse ancestry. Significant odds ratios (ORs) for lung cancer and difficulty quitting smoking were observed in both UKBB and AoU. For lung cancer, the ORs for individuals in the highest risk group (top 20% versus bottom 20%) were 1.85 (95% CI: 1.58 - 2.18) in UKBB and 2.39 (95% CI: 1.93 - 2.97) in AoU. For difficulty quitting smoking, the ORs (top 33% versus bottom 33%) were 1.36 (95% CI: 1.32 - 1.41) in UKBB and 1.32 (95% CI: 1.28 - 1.36) in AoU. Our PRS-based intervention model leverages large-scale genetic data for robust risk assessment across populations. This model will be evaluated in two cluster-randomized clinical trials aimed at motivating health behavior changes in high-risk patients of diverse ancestry. This pioneering approach integrates genomic insights into primary care, promising improved outcomes in cancer prevention and tobacco treatment.

Respirable crystalline silica and lung cancer in community-based studies: impact of job-exposure matrix specifications on exposure-response relationships.

The quantitative job-exposure matrix SYN-JEM consists of various dimensions: job-specific estimates, region-specific estimates, and prior expert ratings of jobs by the semi-quantitative DOM-JEM. We analyzed the effect of different JEM dimensions on the exposure-response relationships between occupational silica exposure and lung cancer risk to investigate how these variations influence estimates of exposure by a quantitative JEM and associated health endpoints. Using SYN-JEM, and alternative SYN-JEM specifications with varying dimensions included, cumulative silica exposure estimates were assigned to 16 901 lung cancer cases and 20 965 controls pooled from 14 international community-based case-control studies. Exposure-response relationships based on SYN-JEM and alternative SYN-JEM specifications were analyzed using regression analyses (by quartiles and log-transformed continuous silica exposure) and generalized additive models (GAM), adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. SYN-JEM and alternative specifications generated overall elevated and similar lung cancer odds ratios ranging from 1.13 (1st quartile) to 1.50 (4th quartile). In the categorical and log-linear analyses SYN-JEM with all dimensions included yielded the best model fit, and exclusion of job-specific estimates from SYN-JEM yielded the poorest model fit. Additionally, GAM showed the poorest model fit when excluding job-specific estimates. The established exposure-response relationship between occupational silica exposure and lung cancer was marginally influenced by varying the dimensions of SYN-JEM. Optimized modelling of exposure-response relationships will be obtained when incorporating all relevant dimensions, namely prior rating, job, time, and region. Quantitative job-specific estimates appeared to be the most prominent dimension for this general population JEM.

Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies.

Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) (Ptrend = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.

Assessment of the EarlyCDT-Lung test as an early biomarker of lung cancer in ever-smokers: A retrospective nested case-control study in two prospective cohorts.

The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample <3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT-Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT-Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI: 0.34-2.30) for a moderate risk EarlyCDT-Lung test result and 1.09 (95% CI: 0.48-2.47) for a high-risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI: 4.6-14) and overall specificity was 92% (95% CI: 87-96) when considering a high-risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI: 7.2-32.1) in subjects with blood drawn up to 1year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT-Lung test in identifying the high-risk subjects in ever-smokers for lung cancer screening in the EPIC and NSHDS cohorts.

Exploration of occupations as risk factors for lung cancer in hierarchical and penalization penalized regression models accounting for multiple known exposures

Background and aim: Traditional occupational epidemiological analysis typically emphasize on disease risks associated with specific single exposures or single occupations. We used hierarchical and regularization models to explore occupational risks at the job-title level associated with lung cancer while accounting for exposures to multiple known lung carcinogens. Methods: We pooled lung cancer case-control study subjects from 14 European and Canadian studies. Associations between ever employment in 1,288 five-digit ISCO-68 occupations and lung cancer were screened using two approaches: Bayesian hierarchical and LASSO penalized regressions. Both modeling approaches account for age, smoking, sex, study, and fully quantitative exposures to six known occupational lung carcinogens: asbestos, chromium, diesel engine exhaust, nickel, PAHs, and silica. False positive findings in the Bayesian hierarchical and LASSO models were controlled using horseshoe priors and stability selection, respectively. Lung cancer odds ratios for selected occupations were estimated using unconditional logistic regression model with identical covariates. Results: Our final analyses included 16,901 lung cancer cases and 20,965 controls. There were notable overlaps in jobs selected by the hierarchical and penalization modeling approaches. Occupations selected by both modeling approaches with positive associations with lung cancer after controlling for known exposures include carpenters (OR: 1.77; 95CI: 1.36, 2.33) and construction bricklayers (OR: 1.40; 95CI: 1.17, 1.67). Similarly selected occupations but with negative associations with lung cancer include secondary school teachers (OR: 0.36; 95CI: 0.23, 0.55), production managers (OR: 0.65; 95CI: 0.53, 0.79), and government executive officials (OR: 0.7; 95% CI: 0.61, 0.79). Conclusion: We demonstrated viable agnostic approaches in identifying employment risk factors for lung cancer. Future work involves investigations of factors that contribute to the observed elevated or lower cancer risks, which may involve gaps in current exposure assessment and modeling framework, and/or exposures to other lung carcinogens yet to be elucidated.

Occupational and environmental asbestos exposure and the risk of lung cancer in Korea: A case-control study in South Chungcheong Province of Korea.

Despite the use of large amounts of asbestos in the 1990s, few studies have been conducted in Korea on occupational and environmental asbestos exposure and lung cancer risk. The main aim of this study was to estimate the risk of lung cancer development caused by occupational and environmental asbestos exposures in residents of South Chungcheong Province, where about half of the asbestos mines in Korea operated. We conducted a case-control study, for which the information on asbestos exposure history and demographic characteristics was provided by the Environmental Health Center for asbestos of Soonchunhyang University Cheonan Hospital. After adjusting for all covariates, the odds ratios for lung cancer tended to increase with higher exposure probability for both occupational as well as environmental asbestos. The relative risk of occupational asbestos exposure was higher than that of environmental exposure; the interaction of co-exposure was not statistically significant. The estimated means of the latency period were significantly shorter in participants who were engaged in the production of asbestos-containing products and in those who lived near asbestos industries as compared to other groups.

Excess Risk of Lung Cancer Among Agriculture and Construction Workers in Indonesia.

Background:In Indonesia, many occupations and industries involve a variety of hazardous and toxic materials. The ILO estimates that about 21.1% of the tracheal, bronchial, and lung cancer deaths among men were attributable to workplace hazardous substances. This study investigated the relationship between occupations or workplace exposure and the risk of lung cancer in the country. The results will help determine how Indonesia can best mitigate the risk for its workers.Objectives:This case-control study utilizes the Indonesian Standard of Industrial Classification (IndSIC) 2015 with the aim of exploring the risk of lung cancer among Indonesian workers.Methods:The study included patients aged 35 years old or older receiving thoracic CT at the radiology department of Persahabatan Hospital. The cases were histological-confirmed primary lung cancers, while the controls were negative thoracic CT scan for lung cancer. The subjects’ job titles and industries were classified according to IndSIC 2015 and blind to the patient’s grouping as a case or control. Logistic regression was used to determine the odds ratios for lung cancer among all sections and some divisions or groups of IndSIC 2015.Findings:The mean age was 58.1 (±10.23) years for lung cancer patients and 54.5 (±10.23) years for controls. The majority of subjects (19.6%) worked in Section G (Wholesale and retail trade; repair of motor vehicles and motorcycle). After adjusting for age, gender, level of education, and smoking habit, the risk of lung cancer was nearly three-times higher (OR = 2.8, 95% CI = 1.11–7.02) in workers of Division A01 (crop, animal production, and hunting) and two-times higher (OR = 1.9, 95% CI = 1.05–3.46) in workers of Section F (construction) compared to the workers in other sections or divisions.Conclusions:The excess risk of lung cancer among certain categories of workers confirms the need for improved policy, monitoring, and control of occupational exposure for primary cancer prevention and workers’ compensation purposes.

Cumulative cigarette tar exposure and lung cancer risk among Japanese smokers.

Tar concentration in cigarette brands is chronologically decreasing in the USA and Japan. However, studies investigating lung cancer risk with cumulative tar exposure in Western and Asian countries are insufficient. To investigate the risk of lung cancer with cumulative cigarette tar exposure, we conducted a case-control study among Japanese current smokers. This study used data from the US-Japan lung cancer joint study in 1993-1998. A total of 282 subjects with histologically confirmed lung cancer and 162 hospital and 227 community controls were included in the study, and two control groups were combined. The information regarding tar concentration was obtained from the published documents and additional estimation using the equation of regression. Cumulative tar concentration was calculated by multiplying the annual value of brand-specific tar concentration by years of smoking. The odds ratios and 95% confidence intervals for lung cancer with cumulative tar exposure were estimated using a logistic model. The odds ratios for lung cancer with both lower (1-59.8×105mg) and higher (>59.8×105mg) total cumulative tar exposure were statistically significant (3.81, 2.23-6.50 and 11.64, 6.56-20.67, respectively) with increasing trend (P<0.001). The stratification analysis showed higher odds ratios in subjects with higher cumulative tar exposure regardless of inhalation, duration of smoking filtered cigarettes and histological type. This study showed that cumulative tar exposure is a dose-dependent indicator for lung cancer risk, and low-tar exposure was still associated with increased cancer risk.

Diesel Engine Exhaust Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Exposure-Response Analysis of 14 Case-Control Studies.

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes.Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations.Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men.Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 μg/m3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined.Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.

P2.10-05 Indoor Radon and Lung Cancer Risk. A Pooling Study on the Second Risk Factor for Lung Cancer

Residential radon is the second risk factor of lung cancer following tobacco consumption, according to WHO (World Health Organization) and United States EPA statements. It is recognized as the first cause of lung cancer in never-smokers by both organizations. Nevertheless, case-control studies performed in radon prone areas are still scarce and with limited sample sizes. We aim to know the relationship between residential radon and lung cancer risk in a study performed in a radon-prone area, and where inhabitants live for a long time in the same dwelling. We have pooled results from 5 different case-control studies performed in the same geographical area to assess the relationship between indoor radon and lung cancer. One of these studies was focused specifically in never smokers and other in Small Cell Lung Cancer. All cases and controls were older than 30 and cases had a confirmed diagnosis of lung cancer. Controls were selected for attending hospital for trivial surgery. Controls were selected through a frequency-based sampling based on age and gender distribution of cases. The information and questionnaires collected was the same in all studies, with special focus on tobacco consumption. Radon devices of an alpha track type were placed at the participants’ homes for at least three months. Odds Ratios of lung cancer due to radon exposure have been calculated adjusted by age, gender, and tobacco consumption. We included 1691 cases and 1698 controls. Median age was 63 and 67, respectively, and females comprised 33% of both cases and controls. Adenocarcinoma was the most frequent histology (43%) and participants lived a median of 30 years in the same dwelling. The table show the risk of lung cancer due to radon exposure. Residential radon is a relevant risk factor for lung cancer, even below concentrations established as safe by USEPA and WHO.

Exposure to Welding Fumes, Hexavalent Chromium, or Nickel and Risk of Lung Cancer.

To investigate the risk of lung cancer after exposure to welding fumes, hexavalent chromium (Cr(VI)), and nickel, we analyzed 3,418 lung cancer cases and 3,488 controls among men from 2 German case-control studies (1988-1996). We developed a welding-process exposure matrix from measurements of these agents, and this was linked with welding histories from a job-specific questionnaire to calculate cumulative exposure variables. Logistic regression models were fitted to estimate odds ratios with confidence intervals conditional on study, and they adjusted for age, smoking, and working in other at-risk occupations. Additionally, we mutually adjusted for the other exposure variables under study. Overall, 800 cases and 645 controls ever worked as regular or occasional welders. Odds ratios for lung cancer with high exposure were 1.55 (95% confidence interval (CI): 1.17, 2.05; median, 1.8 mg/m3 × years) for welding fumes, 1.85 (95% CI: 1.35, 2.54; median, 1.4 μg/m3 × years) for Cr(VI), and 1.60 (95% CI: 1.21, 2.12; median, 9 μg/m3 × years) for nickel. Risk estimates increased with increasing cumulative exposure to welding fumes and with increasing exposure duration for Cr(VI) and nickel. Our results showed that welding fumes, Cr(VI), and nickel might contribute independently to the excess lung cancer risk associated with welding. However, quantitative exposure assessment remains challenging.

Abstract 1593: Genetic interactions in lung cancer using machine-learning approaches in genome-wide association studies

Abstract Genome-wide association studies (GWAS) consisting of hundreds of thousands or millions of single nucleotide polymorphisms (SNPs) have presented the complex inheritance patterns of disease/trait. Although GWAS have identified thousands of SNPS associated with diseases, few studies have explored interactions among these SNPs that may influence disease risks. Machine learning applications can identify SNPs that influence disease risk through interactions and define how these SNPs jointly influence disease risks. Tree-based machine-learning applications; classification and regression trees (CART) and random forest (RF) methods, have become increasingly popular and convenient tools for understanding interactions influencing disease development. Here we apply these methods to understand the genetic architecture of lung cancer. To elucidate the SNP-SNP interactions that influence lung cancer risk, we applied supervised tree-based approaches using 18,444 cases and 14,027 controls from lung cancer OncoArray GWAS data that is the largest lung cancer GWAS so far. To reduce the space of SNPs to consider in modeling, we first selected the SNPs very significantly (p&amp;lt;0.00001) associated with lung cancer risk. Random Forests, which consists of systematically fitting classification trees, was run 1,000 times to identify the most influential SNPs that jointly influence lung cancer risk. Subsequently we applied a classification tree approach to summarize interactions that predict risk. The final parsimonious tree included effects from genetic variants in rs55781567(CHRNA5): rs452384(CLPTM1L): rs9258608(LOC105375010): rs6154144(DNAJC5): rs116506680(HLA-G): rs9271365(near HLADQA1): rs421629(CLPTM1L). The nodes of this tree had Odds ratios for lung cancer ranging from 0.87 to 1.63. Machine-learning approaches in genomics can provide an important genetic mechanism in lung cancer development. Citation Format: Jinyoung Byun, Younghun Han, Christopher I. Amos. Genetic interactions in lung cancer using machine-learning approaches in genome-wide association studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1593.

The Relation between Polymorphisms in Exon 5 and Exon 6 of GSTP1 Gene and the Risk of Lung Cancer in Iranian People

Objective:The GSTP1 gene, which is located on chromosome 11q13, consists of 7 exons and 6 introns. There are two polymorphisms in GSTP1 that have been exposed to a transposition for codon 105 (Ile/Val) and 114 (Ala/Val) in exons 5 and 6, which have been studied previously in relation to lung cancer. Since the level of GSTP1 expression in lung tissues and other human epithelial tissues is high, GSTP1Val-105 polymorphism is recognized as a sensitive factor for tobacco-related cancers, especially lung cancer.Methods:One hundred and twenty tissue block samples of patients with lung cancers and 120 peripheral blood samples of the control group were obtained from two referral cancer centers in Tehran, Iran, from 2011 to 2016. Genomic DNA was extracted from tissue blocks and buffy coat of study cases to detect SNP of GSTP1 gene using Tetra-primer ARMS-PCR.Results:There was a notable correlation between the incidence of lung cancer and variant Val105 (P-value=0.001; OR=2/6; 95% CI=1.49-4.53) and Ile105 (P-value=0.003; OR=0.41; 95% CI=0.23-0.73). The odds ratio for lung cancer in the homozygous Ile105/Ile105 genotype was 3.56 times higher than that of individual with heterozygous Ile105/Val105 (P-value<0.001; OR=3/56; 95% CI=1.826-6.934) genotype, that was statistically significant. Furthermore, the results showed that there was no significant correlation between Ala114/Val114 genotypes and lung cancer. The BC (P-value=0.007; OR=0.16; 95% CI=0.04-0.61) and AA (P=0.001) genotypes were statistically significant (P-value <0.05); and for those who had AA genotype, the odds ratio was almost six times higher than those with BC genotype.Conclusions:The study of GSTP1 polymorphisms indicated that unlike the polymorphism in exon 5, the GSTP1 exon 6 polymorphism correlated with the lung cancer risk in the select group of Iranian people. Likewise, the potential use of this genetic polymorphism as a lung cancer predictor is confirmed.

Abstract 3240: Radon exposure, lung cancer, and respiratory outcomes in a cohort of former and current smokers: An ecologic analysis

Abstract Background and Objective: Residential radon-222 decay product exposure is the second leading cause of lung cancer overall and the leading cause among nonsmokers. The objective of our study was to assess the potential contribution of radon exposure to lung cancer risk and risk of other respiratory conditions, including chronic obstructive pulmonary disease (COPD), that predispose subjects to lung cancer risk. Methods: Participants were 50- to 79-year-old current and former smokers recruited through the Pittsburgh Lung Screening Study (PLuSS) between January 2002 and April 2005. For the current analysis, we considered a subset of 3,070 (out of 3,654) PLuSS participants living in a six-county area of southwestern Pennsylvania at the time of enrollment. We obtained estimates of residential (basement) radon exposure from the PA Department of Environmental Protection at the zip code level for each of the six counties. These estimates were mean radon concentrations calculated from measurements made at individual residences between 1990 and 2016. We linked each study participant to the mean radon concentration in their zip code and conducted adjusted logistic regressions to explore associations with tertiles of increasing radon exposure and risk of lung cancer, COPD, and emphysema. Models were adjusted for age, sex, individual-level smoking status (former or current), the number of cigarettes smoked per day, and the number of years participants smoked. Results: Mean radon levels for the six-county area ranged from 2 to 16 pCi/L. Comparing the third to the first tertile of radon exposure, the odds ratio for lung cancer was 1.10 (95% CI: 0.77-1.57) and not statistically significant. However, higher radon levels were positively associated with increased odds of COPD diagnosis determined at baseline (odds ratio: 1.19, 95% CI: 0.98-1.43, p: 0.07). In linear regression models using baseline spirometry measurements (specifically, the FEV1/FVC ratio) as the outcome, increasing mean radon levels were associated with decreased lung function (β: -139, p: 0.003). In the PLuSS cohort, lung cancer risk decreases as FEV1/FVC ratios increase (i.e., as lung function improves), after accounting for smoking history (odds ratio: 0.78, 95% CI: 0.68-0.89, p: 0.0002). Conclusions: As COPD is an important predisposing factor for respiratory health, lung cancer development, and overall survival, this potential association between residential radon level and COPD risk warrants additional follow-up. Future work will include using more granular radon measurements to characterize exposure as well as to capture potential changes in exposure status over time. Citation Format: Shaina L. Stacy, Linda Robertson, Renwei Wang, David O. Wilson, Jian-Min Yuan. Radon exposure, lung cancer, and respiratory outcomes in a cohort of former and current smokers: An ecologic analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3240.

PCDHGA12 methylation biomarker in bronchial washing specimens as an adjunctive diagnostic tool to bronchoscopy in lung cancer.

The use of bronchoscopy is central to the diagnosis of lung cancer. However, the sensitivity of bronchoscopy is low. In addition, bronchial washing cytology, which is a routine adjunctive test, does not significantly improve the performance of bronchoscopy owing to its low sensitivity. To enhance the diagnostic performance of bronchoscopy, the protocadherin GA12 (PCDHGA12) methylation biomarker in bronchial washings was introduced as a novel adjunctive diagnostic test. A total of 98 patients who underwent bronchoscopy owing to suspicion of lung cancer were analyzed. Cytological examination and PCDHGA12 methylation biomarker testing of the bronchial washing fluid were performed. The performance of the tests was analyzed. The final diagnosis in 60 patients was lung cancer and in 38 patients was benign disease. The PCDHGA12 methylation biomarker had a sensitivity of 75.0%, a specificity of 78.9% and a positive predictive value (PPV) of 84.9%, whereas cytological assessment had a sensitivity of 45.0%, a specificity of 92.1% and a PPV of 90%. Patients with positive PCDHGA12 methylation test had an odds ratio for lung cancer of 11.25 (confidence interval, 4.25-29.8) compared with negative subjects. The combination of the two tests exhibited an increased sensitivity (83.3%), a specificity of 71.1% and a PPV of 82.0%. Furthermore, considering the non-diagnostic bronchoscopy group alone, the test demonstrated a sensitivity of 61.9% and a specificity of 78.9%. The results of the present study demonstrated that PCDHGA12 methylation, as a lung cancer biomarker in bronchial washings, may be a used as an adjunctive test to bronchoscopy.

Mortality Among Hardmetal Production Workers: UK Cohort and Nested Case-Control Studies.

The aim of this study was to characterize the mortality at two hardmetal production factories in the United Kingdom as part of an international study. Standardized mortality ratios (SMRs) were calculated on the basis of mortality rates for England and Wales, and local rates. A nested case-control study of lung cancer was undertaken. The cohort comprised 1538 workers, with tracing complete for 94.4%. All-cause mortality was statistically significantly low for all cancers and nonmalignant respiratory disease, and for lung cancer was nonsignificantly low. The SMR for lung cancer for maintenance workers was elevated, based on only six deaths. The odds ratio for lung cancer per year of exposure to hardmetal was 0.93 (0.76 to 1.13). In this small study, there is no evidence to support that working in the UK hardmetal manufacturing industry increased mortality from any cause including lung cancer.

Serum folate concentration and the incidence of lung cancer.

BackgroundLung cancer is a leading cause of cancer-related mortality globally. Folate helps to maintain DNA integrity and to regulate gene expression. Serum folate levels may affect the risk of several cancers, including lung cancer. In this study we evaluated the association between serum folate concentration and variations in genes involved in folate metabolism with lung cancer incidence in Poland.MethodsThe study included 366 lung cancer patients and 366 control subjects. We measured serum folate concentration and genotyped six variants in MTHFR, MTR and MTRR genes. The odds ratios of being diagnosed with lung cancer were calculated using conditional univariable and multivariable logistic regression with respect to folate level and genotypes.ResultsThe mean serum folate level was lower in lung cancer cases than in control group (20.07 nmol/l vs. 22.52 nmol/l, p = 0.002). The odds ratio for lung cancer declined with increasing serum content of the folate. The folate concentration of >25.71 nmol/l (IVth quartile) in comparison to <15.92 nmol/l (Ist quartile) was associated with an odds ratio of 0.61 (95%CI 0.40–0.95, p = 0.03). The analysis of variations in MTHFR, MTR and MTRR genes did not reveal any significant difference between lung cancer cases and controls in univariable and multivariable analyses.ConclusionIn this case-control study, lower serum folate concentrations were associated with a higher risk of lung cancer diagnosis. Although previous findings have been somewhat mixed, our results add to the evidence that circulating folate levels may be an indicator of lung cancer risk.

Lung and stomach cancer associations with groundwater radon in North Carolina, USA.

The risk of indoor air radon for lung cancer is well studied, but the risks of groundwater radon for both lung and stomach cancer are much less studied, and with mixed results. Geomasked and geocoded stomach and lung cancer cases in North Carolina from 1999 to 2009 were obtained from the North Carolina Central Cancer Registry. Models for the association with groundwater radon and multiple confounders were implemented at two scales: (i) an ecological model estimating cancer incidence rates at the census tract level; and (ii) a case-only logistic model estimating the odds that individual cancer cases are members of local cancer clusters. For the lung cancer incidence rate model, groundwater radon is associated with an incidence rate ratio of 1.03 [95% confidence interval (CI) = 1.01, 1.06] for every 100 Bq/l increase in census tract averaged concentration. For the cluster membership models, groundwater radon exposure results in an odds ratio for lung cancer of 1.13 (95% CI = 1.04, 1.23) and for stomach cancer of 1.24 (95% CI = 1.03, 1.49), which means groundwater radon, after controlling for multiple confounders and spatial auto-correlation, increases the odds that lung and stomach cancer cases are members of their respective cancer clusters. Our study provides epidemiological evidence of a positive association between groundwater radon exposure and lung cancer incidence rates. The cluster membership model results find groundwater radon increases the odds that both lung and stomach cancer cases occur within their respective cancer clusters. The results corroborate previous biokinetic and mortality studies that groundwater radon is associated with increased risk for lung and stomach cancer.

Development of APE1 enzymatic DNA repair assays: low APE1 activity is associated with increase lung cancer risk.

The key role of DNA repair in removing DNA damage and minimizing mutations makes it an attractive target for cancer risk assessment and prevention. Here we describe the development of a robust assay for apurinic/apyrimidinic (AP) endonuclease 1 (APE1; APEX1), an essential enzyme involved in the repair of oxidative DNA damage. APE1 DNA repair enzymatic activity was measured in peripheral blood mononuclear cell protein extracts using a radioactivity-based assay, and its association with lung cancer was determined using conditional logistic regression with specimens from a population-based case-control study with 96 lung cancer cases and 96 matched control subjects. The mean APE1 enzyme activity in case patients was 691 [95% confidence interval (CI) = 655-727] units/ng protein, significantly lower than in control subjects (mean = 793, 95% CI = 751-834 units/ng protein, P = 0.0006). The adjusted odds ratio for lung cancer associated with 1 SD (211 units) decrease in APE1 activity was 2.0 (95% CI = 1.3-3.1; P = 0.002). Comparison of radioactivity- and fluorescence-based assays showed that the two are equivalent, indicating no interference by the fluorescent tag. The APE1Asp148Glu SNP was associated neither with APE1 enzyme activity nor with lung cancer risk. Taken together, our results indicate that low APE1 activity is associated with lung cancer risk, consistent with the hypothesis that 'bad DNA repair', rather than 'bad luck', is involved in cancer etiology. Such assays may be useful, along with additional DNA repair biomarkers, for risk assessment of lung cancer and perhaps other cancers, and for selecting individuals to undergo early detection techniques such as low-dose CT.

Elevated lung cancer in younger adults and low concentrations of arsenic in water.

Arsenic concentrations greater than 100 µg/L in drinking water are a known cause of cancer, but the risks associated with lower concentrations are less well understood. The unusual geology and good information on past exposure found in northern Chile are key advantages for investigating the potential long-term effects of arsenic. We performed a case-control study of lung cancer from 2007 to 2010 in areas of northern Chile that had a wide range of arsenic concentrations in drinking water. Previously, we reported evidence of elevated cancer risks at arsenic concentrations greater than 100 µg/L. In the present study, we restricted analyses to the 92 cases and 288 population-based controls who were exposed to concentrations less than 100 µg/L. After adjustment for age, sex, and smoking behavior, these exposures from 40 or more years ago resulted in odds ratios for lung cancer of 1.00, 1.43 (90% confidence interval: 0.82, 2.52), and 2.01 (90% confidence interval: 1.14, 3.52) for increasing tertiles of arsenic exposure, respectively (P for trend = 0.02). Mean arsenic water concentrations in these tertiles were 6.5, 23.0, and 58.6 µg/L. For subjects younger than 65 years of age, the corresponding odds ratios were 1.00, 1.62 (90% confidence interval: 0.67, 3.90), and 3.41 (90% confidence interval: 1.51, 7.70). Adjustments for occupation, fruit and vegetable intake, and socioeconomic status had little impact on the results. These findings provide new evidence that arsenic water concentrations less than 100 µg/L are associated with higher risks of lung cancer.