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.

• Klíčová slova
• diesel exhaust, epidemiology, lung neoplasms, occupational exposure,
• MeSH
• adenokarcinom plic epidemiologie   MeSH
• dospělí MeSH
• inhalační expozice MeSH
• kouření cigaret epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom epidemiologie   MeSH
• nádory plic epidemiologie   MeSH
• odds ratio MeSH
• pracovní expozice statistika a číselné údaje   MeSH
• senioři MeSH
• sexuální faktory MeSH
• spinocelulární karcinom epidemiologie   MeSH
• uhlík MeSH
• velkobuněčný karcinom epidemiologie   MeSH
• výfukové emise vozidel * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Kanada epidemiologie   MeSH
• Názvy látek
• uhlík MeSH
• výfukové emise vozidel * MeSH

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes.Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.

• Klíčová slova
• crystalline silica, lung cancer, occupational exposure,
• MeSH
• adenokarcinom plic epidemiologie   MeSH
• dospělí MeSH
• inhalační expozice MeSH
• kouření cigaret MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom epidemiologie   MeSH
• nádory plic epidemiologie   patologie   MeSH
• oxid křemičitý * MeSH
• pracovní expozice statistika a číselné údaje   MeSH
• senioři MeSH
• silikóza epidemiologie   MeSH
• spinocelulární karcinom epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Kanada epidemiologie   MeSH
• Názvy látek
• oxid křemičitý * MeSH

AIM: To compare survival outcomes in patients with non-small cell lung cancer (NSCLC) treated with modern-era drugs (antifolates, antiangiogenics, tyrosine kinase and anaplastic lymphoma kinase inhibitors, immunotherapy) with treatment initiation in 2011-12 and 2015-16, respectively. PATIENTS AND METHODS: Prospective data from Czech TULUNG Registry (960 patients from 2011-12 and 512 patients from 2015-16) were analyzed. Kaplan-Meier analysis was used to estimate overall survival (OS) and progression-free survival (PFS); Cox proportional hazards model to assess factors associated with 2-year survival. RESULTS: Survival at 2 years was more frequent in cohort 2015-16 compared to cohort 2011-12 (43.2% vs. 24% for adenocarcinoma; p<0.001 and 28.7% vs. 11.8% for squamous-cell lung carcinoma; p=0.002). Assignment to cohort 2015-16 and treatment multilinearity (two or more lines in sequence) were associated with higher probability of 2-year survival (hazard ratio=0.666 and hazard ratio=0.597; p<0.001). Comparison of 2-year survivors from both cohorts showed no differences. CONCLUSION: Survival at 2 years probability in stage IIIB-IV NSCLC doubled between 2011-12 and 2015-16; advanced-stage NSCLC may be considered a chronic disease in a large proportion of patients.

• Klíčová slova
• 2-year survival, Non-small cell lung cancer, chronic disease, modern-era treatment, personalized treatment,
• MeSH
• adenokarcinom plic epidemiologie   mortalita   patologie   terapie   MeSH
• chronická nemoc MeSH
• dospělí MeSH
• kohortové studie MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory plic epidemiologie   mortalita   patologie   terapie   MeSH
• následné studie MeSH
• nemalobuněčný karcinom plic epidemiologie   mortalita   patologie   terapie   MeSH
• prognóza MeSH
• registrace statistika a číselné údaje   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom epidemiologie   mortalita   patologie   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

BACKGROUND: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. METHODS: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. RESULTS: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 × 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. CONCLUSIONS: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci.

• Klíčová slova
• Mendelian Randomization, TERT, chromosome 5p15.33, lung cancer, mediation analysis, telomere length,
• MeSH
• adenokarcinom plic epidemiologie   MeSH
• dlaždicobuněčné karcinomy hlavy a krku epidemiologie   MeSH
• homeostáza telomer genetika   MeSH
• leukocyty metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 5 genetika   MeSH
• mendelovská randomizace MeSH
• nádory hlavy a krku epidemiologie   MeSH
• nádory plic epidemiologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom epidemiologie   MeSH
• telomery metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH