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1.
Int J Cancer ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513294

RESUMO

Although smoking and oxidative stress are known contributors to lung carcinogenesis, their mechanisms of action remain poorly understood. To shed light into these mechanisms, we applied a novel approach using Cys34-adductomics in a lung cancer nested case-control study (n = 212). Adductomics profiles were integrated with DNA-methylation data at established smoking-related CpG sites measured in the same individuals. Our analysis identified 42 Cys34-albumin adducts, of which 2 were significantly differentially abundant in cases and controls: adduct of N-acetylcysteine (NAC, p = 4.15 × 10-3 ) and of cysteinyl-glycine (p = 7.89 × 10-3 ). Blood levels of the former were found associated to the methylation levels at 11 smoking-related CpG sites. We detect, for the first time in prospective blood samples, and irrespective of time to diagnosis, decreased levels of NAC adduct in lung cancer cases. Altogether, our results highlight the potential role of these adducts in the oxidative stress response contributing to lung carcinogenesis years before diagnosis.

2.
Int J Epidemiol ; 48(5): 1493-1504, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31549173

RESUMO

BACKGROUND: DNA methylation changes in peripheral blood have recently been identified in relation to lung cancer risk. Some of these changes have been suggested to mediate part of the effect of smoking on lung cancer. However, limitations with conventional mediation analyses mean that the causal nature of these methylation changes has yet to be fully elucidated. METHODS: We first performed a meta-analysis of four epigenome-wide association studies (EWAS) of lung cancer (918 cases, 918 controls). Next, we conducted a two-sample Mendelian randomization analysis, using genetic instruments for methylation at CpG sites identified in the EWAS meta-analysis, and 29 863 cases and 55 586 controls from the TRICL-ILCCO lung cancer consortium, to appraise the possible causal role of methylation at these sites on lung cancer. RESULTS: Sixteen CpG sites were identified from the EWAS meta-analysis [false discovery rate (FDR) < 0.05], for 14 of which we could identify genetic instruments. Mendelian randomization provided little evidence that DNA methylation in peripheral blood at the 14 CpG sites plays a causal role in lung cancer development (FDR > 0.05), including for cg05575921-AHRR where methylation is strongly associated with both smoke exposure and lung cancer risk. CONCLUSIONS: The results contrast with previous observational and mediation analysis, which have made strong claims regarding the causal role of DNA methylation. Thus, previous suggestions of a mediating role of methylation at sites identified in peripheral blood, such as cg05575921-AHRR, could be unfounded. However, this study does not preclude the possibility that differential DNA methylation at other sites is causally involved in lung cancer development, especially within lung tissue.

3.
Occup Environ Med ; 76(12): 901-907, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31537717

RESUMO

OBJECTIVES: In a previous analysis of data from a French population-based case-control study (the Investigation of occupational and environmental CAuses of REspiratory cancers (ICARE) study), 'having ever worked' in wood-related occupations was associated with excess lung cancer risk after adjusting for smoking but not for occupational factors. The present study aimed to investigate the relationship between lung cancer risk and wood dust exposure after adjusting for occupational exposures. METHODS: Data were obtained from 2276 cases and 2780 controls on smoking habits and lifelong occupational history, using a standardised questionnaire with a job-specific questionnaire for wood dust exposure. Logistic regression models were used to calculate ORs and 95% CIs adjusted for age, area of residence, tobacco smoking, the number of job periods and exposure to silica, asbestos and diesel motor exhaust (DME). RESULTS: No significant association was found between lung cancer and wood dust exposure after adjustment for smoking, asbestos, silica and DME exposures. The risk of lung cancer was slightly increased among those who were exposed to wood dust more than 10 years, and had over 40 years since the first exposure. CONCLUSION: Our findings do not provide a strong support to the hypothesis that wood dust exposure is a risk factor for lung cancer. This study showed the importance of taking into account smoking and occupational coexposures in studies on lung cancer and wood dust exposure. Further studies evaluating the level and frequency of exposure during various tasks in woodwork are needed.

4.
BMJ ; 364: k4981, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606716

RESUMO

OBJECTIVES: To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. DESIGN: Nested case-control study. SETTING: 20 population based cohort studies in Asia, Europe, Australia, and the United States. PARTICIPANTS: 5299 patients with incident lung cancer, with individually incidence density matched controls. EXPOSURE: Circulating hsCRP concentrations in prediagnostic serum or plasma samples. MAIN OUTCOME MEASURE: Incident lung cancer diagnosis. RESULTS: A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. CONCLUSIONS: Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma de Células Grandes/sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Fumar/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Ex-Fumantes/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Razão de Chances , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Fumantes/estatística & dados numéricos , Fumar/epidemiologia , Adulto Jovem
5.
Int J Epidemiol ; 48(1): 30-44, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590607

RESUMO

BACKGROUND: Socioeconomic experiences are recognized determinants of health, and recent work has shown that social disadvantages in early life may induce sustained biological changes at molecular level that are detectable later in life. However, the dynamics and persistence of biological embedding of socioeconomic position (SEP) remains vastly unexplored. METHODS: Using the data from the ALSPAC birth cohort, we performed epigenome-wide association studies of DNA methylation changes at three life stages (birth, n = 914; childhood at mean age 7.5 years, n = 973; and adolescence at mean age 15.5 years, n = 974), measured using the Illumina HumanMethylation450 Beadchip, in relation to pregnancy SEP indicators (maternal and paternal education and occupation). RESULTS: Across the four early life SEP metrics investigated, only maternal education was associated with methylation levels at birth, and four CpGs mapped to SULF1, GLB1L2 and RPUSD1 genes were identified [false discovery rate (FDR)-corrected P-value <0.05]. No epigenetic signature was found associated with maternal education in child samples, but methylation levels at 20 CpG loci were found significantly associated with maternal education in adolescence. Although no overlap was found between the differentially methylated CpG sites at different ages, we identified two CpG sites at birth and during adolescence which are 219 bp apart in the SULF1 gene that encodes an heparan sulphatase involved in modulation of signalling pathways. Using data from an independent birth cohort, the ENVIRONAGE cohort, we were not able to replicate these findings. CONCLUSIONS: Taken together, our results suggest that parental SEP, and particularly maternal education, may influence the offspring's methylome at birth and adolescence.

6.
Sci Rep ; 8(1): 16714, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30425263

RESUMO

The majority of lung cancer is caused by tobacco smoking, and lung cancer-relevant epigenetic markers have been identified in relation to smoking exposure. Still, smoking-related markers appear to mediate little of the effect of smoking on lung cancer. Thus in order to identify disease-relevant markers and enhance our understanding of pathways, a wide search is warranted. Through an epigenome-wide search within a case-control study (131 cases, 129 controls) nested in a Norwegian prospective cohort of women, we found 25 CpG sites associated with lung cancer. Twenty-three were classified as associated with smoking (LC-AwS), and two were classified as unassociated with smoking (LC-non-AwS), as they remained associated with lung cancer after stringent adjustment for smoking exposure using the comprehensive smoking index (CSI): cg10151248 (PC, CSI-adjusted odds ratio (OR) = 0.34 [0.23-0.52] per standard deviation change in methylation) and cg13482620 (B3GNTL1, CSI-adjusted OR = 0.33 [0.22-0.50]). Analysis among never smokers and a cohort of smoking-discordant twins confirmed the classification of the two LC-non-AwS CpG sites. Gene expression profiles demonstrated that the LC-AwS CpG sites had different enriched pathways than LC-non-AwS sites. In conclusion, using blood-derived DNA methylation and gene expression profiles from a prospective lung cancer case-control study in women, we identified 25 CpG lung cancer markers prior to diagnosis, two of which were LC-non-AwS markers and related to distinct pathways.

7.
JAMA Oncol ; 4(10): e182078, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30003238

RESUMO

Importance: There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases. Objective: To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria. Design, Setting, and Participants: Prediagnostic samples from 108 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and samples from 216 smoking-matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were used to develop a biomarker risk score based on 4 proteins (cancer antigen 125 [CA125], carcinoembryonic antigen [CEA], cytokeratin-19 fragment [CYFRA 21-1], and the precursor form of surfactant protein B [Pro-SFTPB]). The biomarker score was subsequently validated blindly using absolute risk estimates among 63 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and 90 matched controls from 2 large European population-based cohorts, the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS). Main Outcomes and Measures: Model validity in discriminating between future lung cancer cases and controls. Discrimination estimates were weighted to reflect the background populations of EPIC and NSHDS validation studies (area under the receiver-operating characteristics curve [AUC], sensitivity, and specificity). Results: In the validation study of 63 ever-smoking patients with lung cancer and 90 matched controls (mean [SD] age, 57.7 [8.7] years; 68.6% men) from EPIC and NSHDS, an integrated risk prediction model that combined smoking exposure with the biomarker score yielded an AUC of 0.83 (95% CI, 0.76-0.90) compared with 0.73 (95% CI, 0.64-0.82) for a model based on smoking exposure alone (P = .003 for difference in AUC). At an overall specificity of 0.83, based on the US Preventive Services Task Force screening criteria, the sensitivity of the integrated risk prediction (biomarker) model was 0.63 compared with 0.43 for the smoking model. Conversely, at an overall sensitivity of 0.42, based on the US Preventive Services Task Force screening criteria, the integrated risk prediction model yielded a specificity of 0.95 compared with 0.86 for the smoking model. Conclusions and Relevance: This study provided a proof of principle in showing that a panel of circulating protein biomarkers may improve lung cancer risk assessment and may be used to define eligibility for computed tomography screening.

8.
Int J Epidemiol ; 47(6): 1760-1771, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29901778

RESUMO

Background: Self-reported smoking is the principal measure used to assess lung cancer risk in epidemiological studies. We evaluated if circulating cotinine-a nicotine metabolite and biomarker of recent tobacco exposure-provides additional information on lung cancer risk. Methods: The study was conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies. Pre-diagnostic serum cotinine concentrations were measured in one laboratory on 5364 lung cancer cases and 5364 individually matched controls. We used conditional logistic regression to evaluate the association between circulating cotinine and lung cancer, and assessed if cotinine provided additional risk-discriminative information compared with self-reported smoking (smoking status, smoking intensity, smoking duration), using receiver-operating characteristic (ROC) curve analysis. Results: We observed a strong positive association between cotinine and lung cancer risk for current smokers [odds ratio (OR ) per 500 nmol/L increase in cotinine (OR500): 1.39, 95% confidence interval (CI): 1.32-1.47]. Cotinine concentrations consistent with active smoking (≥115 nmol/L) were common in former smokers (cases: 14.6%; controls: 9.2%) and rare in never smokers (cases: 2.7%; controls: 0.8%). Former and never smokers with cotinine concentrations indicative of active smoking (≥115 nmol/L) also showed increased lung cancer risk. For current smokers, the risk-discriminative performance of cotinine combined with self-reported smoking (AUCintegrated: 0.69, 95% CI: 0.68-0.71) yielded a small improvement over self-reported smoking alone (AUCsmoke: 0.66, 95% CI: 0.64-0.68) (P = 1.5x10-9). Conclusions: Circulating cotinine concentrations are consistently associated with lung cancer risk for current smokers and provide additional risk-discriminative information compared with self-report smoking alone.

9.
PLoS One ; 13(2): e0192999, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29462211

RESUMO

BACKGROUND: An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study. METHODS: Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens. RESULTS: The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53 (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)). CONCLUSION: SES remained a risk factor for lung cancer after adjustment for smoking behavior.


Assuntos
Neoplasias Pulmonares/epidemiologia , Fatores Etários , Idoso , Canadá , Europa (Continente) , Feminino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Razão de Chances , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Classe Social
10.
Am J Ind Med ; 61(3): 216-228, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29281122

RESUMO

BACKGROUND: To investigate the association of lung cancer with occupational exposure to textile dust and specifically to cotton dust in the population-based case-control study ICARE. METHODS: Lifelong occupational history of 2926 cases and 3555 controls was collected using standardized questionnaires, with specific questions for textile dust exposure. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using unconditional logistic regression models controlling for confounding factors including smoking and asbestos exposure. RESULTS: An inverse association between textile dust exposure and lung cancer was found among workers exposed ≥5% of their work time (OR = 0.80, 95%CI = 0.58-1.09), more pronounced for distant exposures (40+ years; up to a 56% reduced risk, statistically significant). The OR of lung cancer was significantly decreased among workers exposed to cotton fibers (OR = 0.70, 95%CI = 0.48-0.97). CONCLUSIONS: Our results provide some evidence of a decreased risk of lung cancer associated with exposure to textile dust, particularly cotton.

11.
Environ Int ; 108: 127-136, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28843141

RESUMO

Long-term exposure to air pollution has been associated with several adverse health effects including cardiovascular, respiratory diseases and cancers. However, underlying molecular alterations remain to be further investigated. The aim of this study is to investigate the effects of long-term exposure to air pollutants on (a) average DNA methylation at functional regions and, (b) individual differentially methylated CpG sites. An assumption is that omic measurements, including the methylome, are more sensitive to low doses than hard health outcomes. This study included blood-derived DNA methylation (Illumina-HM450 methylation) for 454 Italian and 159 Dutch participants from the European Prospective Investigation into Cancer and Nutrition (EPIC). Long-term air pollution exposure levels, including NO2, NOx, PM2.5, PMcoarse, PM10, PM2.5 absorbance (soot) were estimated using models developed within the ESCAPE project, and back-extrapolated to the time of sampling when possible. We meta-analysed the associations between the air pollutants and global DNA methylation, methylation in functional regions and epigenome-wide methylation. CpG sites found differentially methylated with air pollution were further investigated for functional interpretation in an independent population (EnviroGenoMarkers project), where (N=613) participants had both methylation and gene expression data available. Exposure to NO2 was associated with a significant global somatic hypomethylation (p-value=0.014). Hypomethylation of CpG island's shores and shelves and gene bodies was significantly associated with higher exposures to NO2 and NOx. Meta-analysing the epigenome-wide findings of the 2 cohorts did not show genome-wide significant associations at single CpG site level. However, several significant CpG were found if the analyses were separated by countries. By regressing gene expression levels against methylation levels of the exposure-related CpG sites, we identified several significant CpG-transcript pairs and highlighted 5 enriched pathways for NO2 and 9 for NOx mainly related to the immune system and its regulation. Our findings support results on global hypomethylation associated with air pollution, and suggest that the shores and shelves of CpG islands and gene bodies are mostly affected by higher exposure to NO2 and NOx. Functional differences in the immune system were suggested by transcriptome analyses.


Assuntos
Poluentes Atmosféricos/farmacologia , Poluição do Ar , Metilação de DNA/efeitos dos fármacos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Doenças Cardiovasculares/induzido quimicamente , Estudos de Coortes , Exposição Ambiental/análise , Epigenômica , Grupo com Ancestrais do Continente Europeu , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Material Particulado/análise , Estudos Prospectivos , Fuligem/análise
12.
Occup Environ Med ; 74(9): 667-679, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28490662

RESUMO

OBJECTIVES: To investigate the role of occupational exposure to endotoxins in lung cancer in a French population-based case-control study (ICARE (Investigation of occupational and environmental causes of respiratory cancers)). METHODS: Detailed information was collected on the occupational history and smoking habits from 2926 patients with histologically confirmed lung cancer and 3555 matched controls. We evaluated each subject's endotoxin exposure after cross referencing International Standard Classification of Occupations (ISCO) codes (for job tasks) and Nomenclature d'Activités Françaises (NAF) codes (for activity sectors). Endotoxin exposure levels were attributed to each work environment based on literature reports. ORs and 95% CIs were estimated using unconditional logistic regression models and controlled for main confounding factors. RESULTS: An inverse association between exposure to endotoxins and lung cancer was found (OR=0.80, 95% CI 0.66 to 0.95). Negative trends were shown with duration and cumulative exposure, and the risk was decreased decades after exposure cessation (all statistically significant). Lung cancer risk was particularly reduced among workers highly exposed (eg, in dairy, cattle, poultry, pig farms), but also in those weakly exposed (eg, in waste treatment). Statistically significant interactions were shown with smoking, and never/light smokers were more sensitive to an endotoxin effect than heavy smokers (eg, OR=0.14, 95% CI 0.06 to 0.32 and OR=0.80, 95% CI 0.45 to 1.40, respectively, for the quartiles with the highest cumulative exposure, compared with those never exposed). Pronounced inverse associations were shown with adenocarcinoma histological subtype (OR=0.37, 95% CI 0.25 to 0.55 in the highly exposed). CONCLUSIONS: Our findings suggest that exposure to endotoxins, even at a low level, reduces the risk of lung cancer.


Assuntos
Endotoxinas/farmacologia , Neoplasias Pulmonares , Pulmão/efeitos dos fármacos , Exposição Ocupacional , Ocupações , Trabalho , Adenocarcinoma/etiologia , Adenocarcinoma de Pulmão , Idoso , Criação de Animais Domésticos , Estudos de Casos e Controles , Feminino , França , Humanos , Modelos Logísticos , Pulmão/patologia , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fumar/efeitos adversos
13.
Epidemiology ; 28(2): 288-299, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28141674

RESUMO

BACKGROUND: Evidence is limited regarding risk and the shape of the exposure-response curve at low asbestos exposure levels. We estimated the exposure-response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies. METHODS: We pooled 14 case-control studies conducted in 1985-2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends. RESULTS: The fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women. CONCLUSIONS: Our results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure-response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.).


Assuntos
Asbestos , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Adulto , Idoso , Canadá/epidemiologia , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fumar/epidemiologia
14.
Lancet ; 389(10075): 1229-1237, 2017 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-28159391

RESUMO

BACKGROUND: In 2011, WHO member states signed up to the 25 × 25 initiative, a plan to cut mortality due to non-communicable diseases by 25% by 2025. However, socioeconomic factors influencing non-communicable diseases have not been included in the plan. In this study, we aimed to compare the contribution of socioeconomic status to mortality and years-of-life-lost with that of the 25 × 25 conventional risk factors. METHODS: We did a multicohort study and meta-analysis with individual-level data from 48 independent prospective cohort studies with information about socioeconomic status, indexed by occupational position, 25 × 25 risk factors (high alcohol intake, physical inactivity, current smoking, hypertension, diabetes, and obesity), and mortality, for a total population of 1 751 479 (54% women) from seven high-income WHO member countries. We estimated the association of socioeconomic status and the 25 × 25 risk factors with all-cause mortality and cause-specific mortality by calculating minimally adjusted and mutually adjusted hazard ratios [HR] and 95% CIs. We also estimated the population attributable fraction and the years of life lost due to suboptimal risk factors. FINDINGS: During 26·6 million person-years at risk (mean follow-up 13·3 years [SD 6·4 years]), 310 277 participants died. HR for the 25 × 25 risk factors and mortality varied between 1·04 (95% CI 0·98-1·11) for obesity in men and 2 ·17 (2·06-2·29) for current smoking in men. Participants with low socioeconomic status had greater mortality compared with those with high socioeconomic status (HR 1·42, 95% CI 1·38-1·45 for men; 1·34, 1·28-1·39 for women); this association remained significant in mutually adjusted models that included the 25 × 25 factors (HR 1·26, 1·21-1·32, men and women combined). The population attributable fraction was highest for smoking, followed by physical inactivity then socioeconomic status. Low socioeconomic status was associated with a 2·1-year reduction in life expectancy between ages 40 and 85 years, the corresponding years-of-life-lost were 0·5 years for high alcohol intake, 0·7 years for obesity, 3·9 years for diabetes, 1·6 years for hypertension, 2·4 years for physical inactivity, and 4·8 years for current smoking. INTERPRETATION: Socioeconomic circumstances, in addition to the 25 × 25 factors, should be targeted by local and global health strategies and health risk surveillance to reduce mortality. FUNDING: European Commission, Swiss State Secretariat for Education, Swiss National Science Foundation, the Medical Research Council, NordForsk, Portuguese Foundation for Science and Technology.


Assuntos
Mortalidade Prematura , Classe Social , Adulto , Consumo de Bebidas Alcoólicas/mortalidade , Estudos de Coortes , Exercício/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/mortalidade , Fatores de Risco , Fumar/mortalidade
15.
Int J Cancer ; 140(1): 50-61, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27632354

RESUMO

DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre-diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case-control study nested within the EPIC-Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case-control pairs). We validated the top signals in 429 case-control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p-valuepooled = 4 × 10-17 ), cg03636183 in the F2RL3 gene (p-valuepooled = 2 × 10 - 13 ), cg21566642 and cg05951221 in 2q37.1 (p-valuepooled = 7 × 10-16 and 1 × 10-11 respectively), cg06126421 in 6p21.33 (p-valuepooled = 2 × 10-15 ) and cg23387569 in 12q14.1 (p-valuepooled = 5 × 10-7 ). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p-valuesheterogeneity ≤ 1.8 x10 - 7 ), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p-values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack-years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk.


Assuntos
Metilação de DNA , DNA/sangue , Neoplasias Pulmonares/diagnóstico , Fumar/genética , Estudos de Casos e Controles , Detecção Precoce de Câncer , Epigênese Genética , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Masculino , Análise em Microsséries/métodos , Fumar/efeitos adversos
16.
Sci Rep ; 6: 38705, 2016 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-27934951

RESUMO

Consistent evidence is accumulating to link lower socioeconomic position (SEP) and poorer health, and the inflammatory system stands out as a potential pathway through which socioeconomic environment is biologically embedded. Using bloodderived genome-wide transcriptional profiles from 268 Italian participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we evaluated the association between early life, young and later adulthood SEP and the expression of 845 genes involved in human inflammatory responses. These were examined individually and jointly using several inflammatory scores. Our results consistently show that participants whose father had a manual (as compared to nonmanual) occupation exhibit, later in life, a higher inflammatory score, hence indicating an overall increased level of expression for the selected inflammatory-related genes. Adopting a life course approach, these associations remained statistically significant upon adjustment for later-in-life socioeconomic experiences. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated, and were replicated in an independent study. Our study provides additional evidence that childhood SEP is associated with a sustainable upregulation of the inflammatory transcriptome, independently of subsequent socioeconomic experiences. Our results support the hypothesis that early social inequalities impacts adult physiology.


Assuntos
Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Transcriptoma , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Inflamação/genética , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos
17.
J Occup Environ Med ; 58(11): 1137-1143, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27820764

RESUMO

OBJECTIVES: The aim of this study was to explore lung cancer risk among firefighters, with adjustment for smoking. METHODS: We used pooled information from the SYNERGY project including 14 case-control studies conducted in Europe, Canada, New Zealand, and China, with lifetime work histories and smoking habits for 14,748 cases of lung cancer and 17,543 controls. We estimated odds ratios by unconditional logistic regression with adjustment for smoking and having ever been employed in a job known to present an excess risk of lung cancer. RESULTS: There was no increased lung cancer risk overall or by specific cell type among firefighters (n = 190), neither before nor after smoking adjustment. We observed no significant exposure-response relationship in terms of work duration. CONCLUSIONS: We found no evidence of an excess lung cancer risk related to occupational exposure as a firefighter.


Assuntos
Bombeiros , Neoplasias Pulmonares/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Canadá , Estudos de Casos e Controles , China , Europa (Continente) , Humanos , Nova Zelândia , Razão de Chances , Fatores de Risco , Fumar
18.
BMC Cancer ; 16: 395, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27388894

RESUMO

BACKGROUND: The nature of the association between occupational social prestige, social mobility, and risk of lung cancer remains uncertain. Using data from the international pooled SYNERGY case-control study, we studied the association between lung cancer and the level of time-weighted average occupational social prestige as well as its lifetime trajectory. METHODS: We included 11,433 male cases and 14,147 male control subjects. Each job was translated into an occupational social prestige score by applying Treiman's Standard International Occupational Prestige Scale (SIOPS). SIOPS scores were categorized as low, medium, and high prestige (reference). We calculated odds ratios (OR) with 95 % confidence intervals (CI), adjusting for study center, age, smoking, ever employment in a job with known lung carcinogen exposure, and education. Trajectories in SIOPS categories from first to last and first to longest job were defined as consistent, downward, or upward. We conducted several subgroup and sensitivity analyses to assess the robustness of our results. RESULTS: We observed increased lung cancer risk estimates for men with medium (OR = 1.23; 95 % CI 1.13-1.33) and low occupational prestige (OR = 1.44; 95 % CI 1.32-1.57). Although adjustment for smoking and education reduced the associations between occupational prestige and lung cancer, they did not explain the association entirely. Traditional occupational exposures reduced the associations only slightly. We observed small associations with downward prestige trajectories, with ORs of 1.13, 95 % CI 0.88-1.46 for high to low, and 1.24; 95 % CI 1.08-1.41 for medium to low trajectories. CONCLUSIONS: Our results indicate that occupational prestige is independently associated with lung cancer among men.


Assuntos
Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/efeitos adversos , Fumar/efeitos adversos , Mobilidade Social/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fumar/epidemiologia , Fatores Socioeconômicos , Adulto Jovem
19.
J Occup Environ Med ; 58(6): 610-6, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27206119

RESUMO

OBJECTIVES: Lung cancer risk associated with occupational cleaning activities has been investigated in the population-based case-control study ICARE. METHODS: Occupational history was collected by standardized interviews. Jobs were first defined according to the International Standard Classification of Occupations (ISCO) codes and then categorized according to activity sectors. Adjusted odds ratios (ORs) were estimated by unconditional logistic regression, separately for women (619 cases and 760 controls) and men (2265 and 2780). RESULTS: Thirty percent of women and 2.3% of men controls ever held a cleaner or care job. Women who worked as housemaids longer than 7 years showed an OR of 1.76 [95% confidence interval (95% CI) 1.09 to 2.87] with respect to controls. Women employed in domestic service sector for a long time had an OR of 2.06 (95% CI 1.15 to 3.66). CONCLUSION: We confirmed and redefined the association of lung cancer with occupational cleaning, which concerns a considerable proportion of women workers.


Assuntos
Neoplasias Pulmonares/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Ocupações , Idoso , Estudos de Casos e Controles , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
20.
Sci Rep ; 6: 25170, 2016 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-27117519

RESUMO

Lower socioeconomic position (SEP) has consistently been associated with poorer health. To explore potential biological embedding and the consequences of SEP experiences from early life to adulthood, we investigate how SEP indicators at different points across the life course may be related to a combination of 28 inflammation markers. Using blood-derived inflammation profiles measured by a multiplex array in 268 participants from the Italian component of the European Prospective Investigation into Cancer and Nutrition cohort, we evaluate the association between early life, young adulthood and later adulthood SEP with each inflammatory markers separately, or by combining them into an inflammatory score. We identified an increased inflammatory burden in participants whose father had a manual occupation, through increased plasma levels of CSF3 (G-CSF; ß = 0.29; P = 0.002), and an increased inflammatory score (ß = 1.96; P = 0.029). Social mobility was subsequently modelled by the interaction between father's occupation and the highest household occupation, revealing a significant difference between "stable Non-manual" profiles over the life course versus "Manual to Non-manual" profiles (ß = 2.38, P = 0.023). Low SEP in childhood is associated with modest increase in adult inflammatory burden; however, the analysis of social mobility suggests a stronger effect of an upward social mobility over the life course.


Assuntos
Biomarcadores/sangue , Fator Estimulador de Colônias de Granulócitos/sangue , Inflamação/sangue , Adulto , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Mobilidade Social
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