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BACKGROUND: Increased lung-cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits, and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects (NDE) and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately as well as by multiple quantitative bias analysis, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung-cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung-cancer risk in the multiple bias analysis. Lung-cancer risks remained increased for lower SES groups, with higher risks in men [4th versus 1st (highest) SES quartile: CDE 1.50 (SI 1.32-1.69)] than women [CDE 1.20 (SI 1.01-1.45)]. NDE were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung-cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.
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The aim of our study is to evaluate the relationship between sociodemographic and clinical characteristics of individuals with Colorectal Cancer (CRC), tumour-intrinsic characteristics and treatment received with health-related quality of life (HRQoL). METHODS: Cross-sectional analysis of data from 805 survivors from the MCC study was conducted. HRQoL was assessed through a general and specific questionnaire, SF-12 and FCSI (Colorectal Symptom Index). Statistical analyses were performed with linear regression with adjustment for sociodemographic variables, stage at diagnosis and histological grade. RESULTS: Participants had survived a median of 7.9 years from diagnosis (IQR 7.1-8.5 years). Age at diagnosis, sex and area showed a clear association with HRQoL in both physical and mental dimensions of the SF-12 questionnaire. A direct association between CRC recurrence was also found in the PCS-12 and MCS-12 dimensions and radical surgery in the PCS-12. Regarding the scores in FCSI questionnaire, statistically significant differences were observed by sex, age and area, with older women being the most impaired (p < 0.001). CONCLUSIONS: Age, sex and area was associated with lower scores of HRQoL among CRC survivors. Knowing the determinants related to HRQoL would allow us to lay the groundwork to develop strategies that help reduce morbidity and mortality, relapses and increase HRQoL.
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BACKGROUND: Radon is a radioactive gas and a major risk factor for lung cancer (LC). METHODS: We investigated the dose-response relationship between radon and LC risk in the International Lung Cancer Consortium with 8927 cases and 5562 controls from Europe, North America, and Israel, conducted between 1992 and 2016. Spatial indoor radon exposure in the residential area (sIR) obtained from national surveys was linked to the participants' residential geolocation. Parametric linear and spline functions were fitted within a logistic regression framework. RESULTS: We observed a non-linear spatial-dose response relationship for sIR < 200 Bq/m3. The lowest risk was observed for areas of mean exposure of 58 Bq/m3 (95% CI: 56.1-59.2 Bq/m3). The relative risk of lung cancer increased to the same degree in areas averaging 25 Bq/m3 (OR = 1.31, 95% CI: 1.01-1.59) as in areas with a mean of 100 Bq/m3 (OR = 1.34, 95% CI: 1.20-1.45). The strongest association was observed for small cell lung cancer and the weakest for squamous cell carcinoma. A stronger association was also observed in men, but only at higher exposure levels. The non-linear association is primarily observed among the younger population (age < 69 years), but not in the older population, which can potentially represent different biological radiation responses. CONCLUSIONS: The sIR is useful as proxy of individual radon exposure in epidemiological studies on lung cancer. The usual assumption of a linear, no-threshold dose-response relationship, as can be made for individual radon exposures, may not be optimal for sIR values of less than 200 Bq/m3.
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Contaminación del Aire Interior , Neoplasias Pulmonares , Radón , Humanos , Radón/efectos adversos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Masculino , Femenino , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/análisis , Persona de Mediana Edad , Anciano , Estudios de Casos y Controles , Contaminantes Radiactivos del Aire/efectos adversos , Contaminantes Radiactivos del Aire/análisis , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/etiología , Factores de Riesgo , Europa (Continente)/epidemiología , Israel/epidemiología , Adulto , Relación Dosis-Respuesta en la Radiación , América del Norte/epidemiologíaRESUMEN
OBJECTIVES: To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study. DESIGN: Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined. SETTING: Children aged 0-18 years from 26 European birth cohorts. PARTICIPANTS: 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood. MAIN OUTCOME MEASURE: Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity) at age 6-18 years. RESULTS: Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3-5 years was not associated with asthma at age 6-18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results. CONCLUSIONS: Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood.
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Asma , Ejercicio Físico , Conducta Sedentaria , Humanos , Niño , Asma/epidemiología , Asma/fisiopatología , Adolescente , Masculino , Preescolar , Europa (Continente)/epidemiología , Femenino , Lactante , Acelerometría , Estudios Longitudinales , Encuestas y Cuestionarios , Volumen Espiratorio Forzado , Espirometría , Recién Nacido , Capacidad Vital , Cohorte de NacimientoRESUMEN
Purpose of review: This review aims to explore the public health approach for Helicobacter pylori Infection Prevention within the Total Worker Health (TWH) framework strategy. Recent findings: The review identifies certain occupations considered high-risk groups for H. pylori infection. It underscores primary, secondary, and tertiary public health preventive measures align with the TWH approach. Within this framework, the role of raising awareness, emphasizing infection control, worker hygiene, risk assessment, and ensuring healthcare accessibility is emphasized. The importance of early detection, treatment, eradication, and a TWH approach emerges as a central theme. The TWH approach offers a holistic perspective, intertwining occupation-related health risks with overall health and well being. Summary: Adopting the TWH approach, coupled with household-based infection control and eradication strategies, can significantly reduce H. pylori prevalence, fostering a healthier workforce and diminishing long-term healthcare costs. The review underscores the importance of recognizing H. pylori as an occupational disease. It calls for further research into the "one-health" perspective on H. pylori transmission dynamics.
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OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Neoplasias Pulmonares , Exposición Profesional , Humanos , Exposición Profesional/análisis , Ocupaciones , Estudios de Casos y Controles , Dióxido de Silicio/análisisRESUMEN
BACKGROUND: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents. OBJECTIVES: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking. METHODS: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI). RESULTS: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8). DISCUSSION: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.
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Amianto , Neoplasias Pulmonares , Exposición Profesional , Hidrocarburos Policíclicos Aromáticos , Masculino , Femenino , Humanos , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/epidemiología , Carcinógenos/toxicidad , Estudios de Casos y Controles , Cromo/toxicidad , Hidrocarburos Policíclicos Aromáticos/toxicidad , Dióxido de Silicio/toxicidad , Pulmón , Amianto/toxicidadRESUMEN
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.
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Neoplasias Pulmonares , Enfermedades Profesionales , Exposición Profesional , Humanos , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/epidemiología , Benceno/toxicidad , Exposición Profesional/efectos adversos , Carcinógenos , Pulmón , Estudios de Casos y Controles , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/epidemiologíaRESUMEN
BACKGROUND: Chronic lymphocytic leukemia (CLL) etiology is poorly understood, and carcinogenic chemicals in drinking and recreational water are candidates. OBJECTIVE: To evaluate the association between drinking-water exposure to trihalomethanes (THMs) and nitrate as well as lifetime swimming pool attendance and CLL. METHODS: During 2010-2013, hospital-based CLL cases and population-based controls were recruited in Spain, providing information on residential histories, type of water consumed and swimming pool attendance. Average THMs and nitrate levels in drinking water were linked to lifetime water consumption. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using mixed models. RESULTS: Final samples for residential tap water analyses and swimming pool attendance analyses were 144 cases/1230 controls and 157 cases/1240 controls, respectively. Mean (SD) values for average lifetime residential brominated THMs and chloroform in tap water (µg/L), and ingested nitrate (mg/day) were 48.1 (35.6), 18.5 (6.7) and 13.7 (9.6) respectively in controls; and 72.9 (40.7), 17.9 (5.4), and 14.1 (8.8) in CLL cases. For each 10 µg/L increase of brominated THMs and chloroform lifetime-average levels, the ORs (95% CI) were 1.22 (1.14, 1.31) and 0.54 (0.34, 0.87), respectively. For each 5 mg/day increase of ingested nitrate, the OR of CLL was 0.91 (0.80, 1.04). The OR of lifetime pool users (vs. non-users) was 2.38 (1.61, 3.52). Upon performing annual frequency of attending pools analysis through categorization, the second and third categories showed an ORs of 2.36 (1.49, 3.72) and 2.40 (1.51, 3.83), respectively, and P-trend of 0.001. IMPACT STATEMENT: This study identifies an association of long-term exposure to THMs in drinking water, at concentrations below the regulatory thresholds and WHO guidelines, and swimming pool attendance, with chronic lymphocytic leukemia (CLL). These unprecedented findings are highly relevant since CLL is an incurable cancer with still unknown etiology and because the widespread exposure to chlorination by-products that remain in drinking and recreational water worldwide. Despite the demonstrated carcinogenicity in animals of several chlorination by-products, little is known about their potential risks on human health. This study makes a significant contribution to the search for environmental factors involved in the etiology of CLL and to the evidence of the health impact of these high prevalent water contaminants.
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Agua Potable , Leucemia Linfocítica Crónica de Células B , Piscinas , Animales , Humanos , Leucemia Linfocítica Crónica de Células B/inducido químicamente , Leucemia Linfocítica Crónica de Células B/epidemiología , Trihalometanos/efectos adversos , Cloroformo , Nitratos/efectos adversos , España/epidemiologíaRESUMEN
BACKGROUND: The COVID-19 pandemic has posed unprecedented challenges, particularly for healthcare workers (HCWs). The prolonged struggles exposed the HCWs to a variety of stressors, potentially leading to burnout. Emotional exhaustion is widely recognized as the core component of burnout. This research aims to conceptualize and develop an emotional exhaustion screening questionnaire through literature review, validation, and accuracy testing. METHOD: A literature review of questionnaires and extraction of items on emotional exhaustion were performed in June 2022. We proceed with the face validity of the items by experts. The items with good content validity ratio and index were selected and reworded to suit the context of HCWs working during the COVID-19 pandemic. A pilot test of the questionnaire was done in the Central University Hospital of Asturias (HUCA) from October to December 2022 with a sample of 148 HCWs from the ORCHESTRA cohort to determine its reliability, convergent validity, and accuracy. RESULTS: Our literature review identified 15 validated questionnaires. After exclusion, 32 items were sent for content validation by experts, yielding five final items that proceeded with the pilot test. Resulting in a Cronbach's alpha-coefficient of .83 for the scale and .78 for dichotomous responses, demonstrating good internal consistency and convergent validity. The result of our accuracy test yielded sensitivity (90.6%) and specificity (91.6%) for the OEEQ scale; and sensitivity (88.7%) and specificity (89.5%) for OEEQ dichotomous responses. CONCLUSION: This study developed and validated the ORCHESTRA Emotional Exhaustion Questionnaire, demonstrating the questionnaire's clarity, relevance, and comprehensibility in screening emotional exhaustion among HCWs.
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COVID-19 , Humanos , Agotamiento Emocional , Pandemias , Reproducibilidad de los Resultados , Personal de Salud , Encuestas y CuestionariosRESUMEN
BACKGROUND: Some researchers have suggested that zinc (Zn) could reduce the risk of prostate cancer (PC). However, research from observational studies on the relationship between PC risk and biomarkers of Zn exposure shows conflicting results. OBJECTIVES: To evaluate the association between toenail Zn and PC, considering tumour extension and aggressiveness, along with a gene-environment approach, exploring the interaction of individual genetic susceptibility to PC in the relationship between toenail Zn and PC. METHODS: In MCC-Spain study we invited all incident PC cases diagnosed in the study period (2008-2013) and recruited randomly selected general population controls. In this report we included 913 cases and 1198 controls with toenail Zn determined by inductively coupled plasma mass spectrometry. To measure individual genetic susceptibility, we constructed a polygenic risk score based on known PC-related single nucleotide polymorphisms. The association between toenail Zn and PC was explored with mixed logistic and multinomial regression models. RESULTS: Men with higher toenail Zn had higher risk of PC (OR quartile 4 vs.1: 1.41; 95% CI: 1.07-1.85). This association was slightly higher in high-grade PC [(ISUP≤2 Relative risk ratio (RRR) quartile 4 vs.1: 1.36; 1.01-1.83) vs. (ISUP3-5 RRR quartile 4 vs.1: 1.64; 1.06-2.54)] and in advanced tumours [(cT1-cT2a RRR quartile 4 vs.1: 1.40; 95% CI: 1.05-1.89) vs. (cT2b-cT4 RRR quartile 4 vs.1: 1.59; 1.00-2.53)]. Men with lower genetic susceptibility to PC were those at higher risk of PC associated with high toenail Zn (OR quartile 4 vs.1: 2.18; 95% CI: 1.08-4.40). DISCUSSION: High toenail Zn levels were related to a higher risk for PC, especially for more aggressive or advanced tumours. This effect was stronger among men with a lower genetic susceptibility to PC.
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Neoplasias de la Próstata , Zinc , Masculino , Humanos , Zinc/análisis , Estudios de Casos y Controles , España/epidemiología , Uñas/química , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/genética , Predisposición Genética a la Enfermedad , Compuestos Orgánicos , Factores de RiesgoRESUMEN
INTRODUCTION: The role of cigarette smoking on breast cancer risk remains controversial, due to its dual carcinogenic-antiestrogenic action. METHODS: In the population-based multi-case-control study (MCC-Spain), we collected epidemiological and clinical information for 1733 breast cancer cases and 1903 controls, including smoking exposure. The association with breast cancer, overall, by pathological subtype and menopausal status, was assessed using logistic and multinomial regression models. RESULTS: Smokers had higher risk of premenopausal breast cancer, particularly if they had smoked ≥30 years (AOR=1.75; 95% CI: 1.04-2.94), although most estimates did not achieve statistical significance. In contrast, among postmenopausal women, smoking was associated with lower risk of breast cancer, mainly in overweight and obese women. The strongest risk reductions were observed among postmenopausal women who had stopped smoking ≥10 years before cancer diagnosis, particularly for HER2+ tumors (AOR=0.28; 95% CI: 0.11-0.68); p for heterogeneity = 0.040). Also, those who had smoked <10 pack-years (AOR=0.68; 95% CI: 0.47-0.98) or 10-25 pack-years (AOR=0.62; 95% CI: 0.42-0.92) during their lifetime were at a reduced risk of all breast cancer subtypes (p for heterogeneity: 0.405 and 0.475, respectively); however, women who had smoked more than 25 pack-years showed no reduced risk. CONCLUSIONS: Menopausal status plays a key role in the relationship between tobacco and breast cancer for all cancer subtypes. While smoking seems to increase the risk in premenopausal woman, it might be associated to lower risk of breast cancer among postmenopausal women with excess weight.
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BACKGROUND: Although physical activity (PA) has been recognized as a favourable factor in the prevention of various diseases, including certain forms of cancer, the relationship between PA and gastric cancer (GC) is not yet fully understood. This study aims to provide data from a pooled analysis of case-control studies within the Stomach cancer Pooling (StoP) Project to estimate the association between leisure-time PA and the occurrence of GC. METHODS: Six case-control studies from StoP project collected data on leisure-time PA, for a total of 2,343 cases and 8,614 controls. Subjects were classified into three leisure-time PA categories, either none/low, intermediate or high, based on study-specific tertiles. We used a two-stage approach. Firstly, we applied multivariable logistic regression models to obtain study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) then, we used a random-effect models to obtain pooled effect estimates. We performed stratified analyses according to demographic, lifestyle and clinical covariates. RESULTS: The meta-analysis showed ORs of GC with no significant differences between intermediate vs low and high vs low PA level (OR 1.05 [95%CI 0.76-1.45]; OR 1.23 [95%CI 0.78-1.94], respectively). GC risk estimates did not strongly differ across strata of selected covariates except for age ≤ 55 years old (high vs low level: OR 0.72 [95%CI 0.55-0.94]) and for control population-based studies (high vs low level: OR 0.79 [95%CI 0.68-0.93]). CONCLUSIONS: No association was found between leisure time PA and GC, apart from a slight suggestion of decreased risk below age 55 and in control population-based studies. These results may reflect specific characteristics of GC at a younger age, or the presence of a cohort effect mediating and interacting with socioeconomic determinants of GC The different distribution of PA levels among hospitalized controls could have led to an underestimated effect of PA on GC risk.
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Neoplasias Gástricas , Humanos , Persona de Mediana Edad , Neoplasias Gástricas/epidemiología , Actividad Motora , Ejercicio Físico , Actividades RecreativasRESUMEN
Pulmonary surfactant is a lipoprotein synthesized and secreted by alveolar type II cells in lung. We evaluated the associations between 200,139 single nucleotide polymorphisms (SNPs) of 40 surfactant-related genes and lung cancer risk using genotyped data from two independent lung cancer genome-wide association studies. Discovery data included 18,082 cases and 13,780 controls of European ancestry. Replication data included 1,914 cases and 3,065 controls of European descent. Using multivariate logistic regression, we found novel SNPs in surfactant-related genes CTSH [rs34577742 C > T, odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.89-0.93, P = 7.64 × 10-9] and SFTA2 (rs3095153 G > A, OR = 1.16, 95% CI = 1.10-1.21, P = 1.27 × 10-9) associated with overall lung cancer in the discovery data and validated in an independent replication data-CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.80-0.96, P = 5.76 × 10-3) and SFTA2 (rs3095153 G > A, OR = 1.14, 95% CI = 1.01-1.28, P = 3.25 × 10-2). Among ever smokers, we found SNPs in CTSH (rs34577742 C > T, OR = 0.89, 95% CI = 0.85-0.92, P = 1.94 × 10-7) and SFTA2 (rs3095152 G > A, OR = 1.20, 95% CI = 1.14-1.27, P = 4.25 × 10-11) associated with overall lung cancer in the discovery data and validated in the replication data-CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.79-0.97, P = 1.64 × 10-2) and SFTA2 (rs3095152 G > A, OR = 1.15, 95% CI = 1.01-1.30, P = 3.81 × 10-2). Subsequent transcriptome-wide association study using expression weights from a lung expression quantitative trait loci study revealed genes most strongly associated with lung cancer are CTSH (PTWAS = 2.44 × 10-4) and SFTA2 (PTWAS = 2.32 × 10-6).
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Neoplasias Pulmonares , Surfactantes Pulmonares , Humanos , Estudio de Asociación del Genoma Completo , Pulmón/metabolismo , Genotipo , Surfactantes Pulmonares/metabolismo , Tensoactivos/metabolismo , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Catepsina H/genética , Catepsina H/metabolismoRESUMEN
Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase-Control (MCC-Spain) study were recruited (2008-2013). The consumption of AS, from table-top sweeteners and artificially sweetened beverages, was assessed through a self-administered and validated food frequency questionnaire (FFQ). Sex-specific quartiles among controls were determined to compare moderate consumers (Asunto(s)
Diabetes Mellitus
, Neoplasias Gástricas
, Masculino
, Femenino
, Humanos
, Edulcorantes/efectos adversos
, Aspartame/efectos adversos
, España/epidemiología
, Neoplasias Gástricas/inducido químicamente
, Neoplasias Gástricas/epidemiología
RESUMEN
BACKGROUND: Nitrate and trihalomethanes (THMs) in drinking water are widespread and are potential human carcinogens. OBJECTIVE: We evaluated the association between drinking-water exposure to nitrate and THMs and prostate cancer. METHODS: During the period 2008-2013, 697 hospital-based incident prostate cancer cases (97 aggressive tumors) and 927 population-based controls were recruited in Spain, providing information on residential histories and type of water consumed. Average nitrate and THMs levels in drinking water were linked with lifetime water consumption to calculate waterborne ingestion. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using mixed models with recruitment area as random effect. Effect modification by tumor grade (Gleason score), age, education, lifestyle, and dietary factors was explored. RESULTS: Mean (±standard deviation) adult lifetime waterborne ingested nitrate (milligrams per day), brominated (Br)-THMs (micrograms per day), and chloroform (micrograms per day) were 11.5 (±9.0), 20.7 (±32.4), and 15.1 (±14.7) in controls. Waterborne ingested nitrate >13.8 vs. <5.5mg/d was associated with an OR of 1.74 (95% CI: 1.19, 2.54) overall, and 2.78 (95% CI: 1.23, 6.27) for tumors with Gleason scores ≥8. Associations were higher in the youngest and those with lower intakes of fiber, fruit/vegetables, and vitamin C. Waterborne ingested THMs were not associated with prostate cancer. Residential tap water levels of Br-THMs and chloroform showed, respectively, inverse and positive associations with prostate cancer. CONCLUSIONS: Findings suggest long-term waterborne ingested nitrate could be a risk factor of prostate cancer, particularly for aggressive tumors. High intakes of fiber, fruit/vegetables and vitamin C may lower this risk. Association with residential levels but not ingested chloroform/Br-THM may suggest inhalation and dermal routes could be relevant for prostate cancer. https://doi.org/10.1289/EHP11391.
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Agua Potable , Neoplasias de la Próstata , Contaminantes Químicos del Agua , Adulto , Masculino , Humanos , Agua Potable/análisis , Nitratos/análisis , Exposición a Riesgos Ambientales/análisis , Trihalometanos/toxicidad , Cloroformo , España/epidemiología , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/epidemiología , Contaminantes Químicos del Agua/análisis , Ácido AscórbicoRESUMEN
OBJECTIVE: Heat exposure and heat stress/strain is a concern for many workers. There is increasing interest in potential chronic health effects of occupational heat exposure, including cancer risk. We examined potential associations of occupational heat exposure and colorectal cancer (CRC) risk in a large Spanish multi-case--control study. METHODS: We analyzed data on 1198 histologically confirmed CRC cases and 2690 frequency-matched controls. The Spanish job-exposure matrix, MatEmEsp, was used to assign heat exposure estimates to the lifetime occupations of participants. Three exposure indices were assessed: ever versus never exposed, cumulative exposure and duration (years). We estimated odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression adjusting for potential confounders. RESULTS: Overall, there was no association of ever, compared with never, occupational heat exposure and CRC (OR 1.09, 95% CI 0.92-1.29). There were also no associations observed according to categories of cumulative exposure or duration, and there was no evidence for a trend. There was no clear association of ever occupational heat exposure and CRC in analysis conducted among either men or women when analyzed separately. Positive associations were observed among women in the highest categories of cumulative exposure (OR 1.81, 95% CI 1.09-3.03) and duration (OR 2.89, 95% CI 1.50-5.59) as well as some evidence for a trend (P<0.05). CONCLUSION: Overall, this study provides no clear evidence for an association between occupational heat exposure and CRC.
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Neoplasias Colorrectales , Enfermedades Profesionales , Exposición Profesional , Masculino , Humanos , Femenino , España/epidemiología , Exposición Profesional/efectos adversos , Modelos Logísticos , Neoplasias Colorrectales/epidemiología , Estudios de Casos y Controles , Enfermedades Profesionales/epidemiología , Factores de RiesgoRESUMEN
There is limited evidence regarding the exposure-effect relationship between lung-cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung-cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case-control studies from Europe and Canada, including 16 901 lung-cancer cases and 20 965 control subjects. A measurement-based job-exposure-matrix estimated job-year-region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects' occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95% CI 1.19-1.47) and 1.29 (95% CI 1.15-1.45) in relation to nickel. Analogous results among women were: 1.04 (95% CI 0.48-2.24) and 1.29 (95% CI 0.60-2.86), respectively. In men, excess lung-cancer risks due to occupational Cr(VI) and nickel exposure were also observed in each stratum of never, former and current smokers. Joint effects of Cr(VI) and nickel with smoking were in general greater than additive, but not different from multiplicative. In summary, relatively low cumulative levels of occupational exposure to Cr(VI) and nickel were associated with increased ORs for lung cancer, particularly in men. However, we cannot rule out a combined classical measurement and Berkson-type of error structure, which may cause differential bias of risk estimates.
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Neoplasias Pulmonares , Exposición Profesional , Masculino , Humanos , Femenino , Níquel/toxicidad , Níquel/análisis , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/epidemiología , Cromo/toxicidad , Cromo/análisis , Estudios de Casos y ControlesRESUMEN
INTRODUCTION: We explored the association of respiratory and cardiometabolic comorbidities with NSCLC overall survival (OS) and lung cancer-specific survival (LCSS), by stage, in a large, multicontinent NSCLC pooled data set. METHODS: On the basis of patients pooled from 11 International Lung Cancer Consortium studies with available respiratory and cardiometabolic comorbidity data, adjusted hazard ratios (aHRs) were estimated using Cox models for OS. LCSS was evaluated using competing risk Grey and Fine models and cumulative incidence functions. Logistic regression (adjusted OR [aOR]) was applied to assess factors associated with surgical resection. RESULTS: OS analyses used patients with NSCLC with respiratory health or cardiometabolic health data (N = 16,354); a subset (n = 11,614) contributed to LCSS analyses. In stages I to IIIA NSCLC, patients with respiratory comorbidities had worse LCCS (stage IA aHR = 1.51, confidence interval [CI]: 1.17-1.95; stages IB-IIIA aHR = 1.20, CI: 1.06-1.036). In contrast, patients with stages I to IIIA NSCLC with cardiometabolic comorbidities had a higher risk of death from competing (non-NSCLC) causes (stage IA aHR = 1.34, CI: 1.12-1.69). The presence of respiratory comorbidities was inversely associated with having surgical resection (stage IA aOR = 0.54, CI: 0.35-0.83; stages IB-IIIA aOR = 0.57, CI: 0.46-0.70). CONCLUSIONS: The presence of either cardiometabolic or respiratory comorbidities is associated with worse OS in stages I to III NSCLC. Patients with respiratory comorbidities were less likely to undergo surgery and had worse LCSS, whereas patients with cardiometabolic comorbidities had a higher risk of death from competing causes. As more treatment options for stages I to III NSCLC are introduced into the practice, accounting for cardiometabolic and respiratory comorbidities becomes essential in trial interpretation and clinical management.
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Carcinoma de Pulmón de Células no Pequeñas , Enfermedades Cardiovasculares , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Pulmón/patología , Comorbilidad , Enfermedades Cardiovasculares/epidemiología , Estadificación de NeoplasiasRESUMEN
Background: The persistence of antibody levels after COVID-19 vaccination has public health relevance. We analyzed the determinants of quantitative serology at 9 months after vaccination in a multicenter cohort. Methods: We analyzed data on anti-SARS-CoV-2 spike antibody levels at 9 months from the first dose of vaccinated HCW from eight centers in Italy, Germany, Spain, Romania and Slovakia. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log antibody level and the corresponding 95% confidence interval (CI), and combined them in random-effects meta-analyses. Finally, we conducted a trend analysis of 1 to 7 months' serology within one cohort. Results: We included 20,216 HCW with up to two vaccine doses and showed that high antibody levels were associated with female sex (p = 0.01), age (RR = 0.87, 95% CI = 0.86-0.88 per 10-year increase), 10-day increase in time since last vaccine (RR = 0.97, 95% CI 0.97-0.98), previous infection (3.03, 95% CI = 2.92-3.13), two vaccine doses (RR = 1.22, 95% CI = 1.09-1.36), use of Spikevax (OR = 1.51, 95% CI = 1.39-1.64), Vaxzevria (OR = 0.57, 95% CI = 0.44-0.73) or heterologous vaccination (OR = 1.33, 95% CI = 1.12-1.57), compared to Comirnaty. The trend in the Bologna cohort, based on 3979 measurements, showed a decrease in mean standardized antibody level from 8.17 to 7.06 (1-7 months, p for trend 0.005). Conclusions: Our findings corroborate current knowledge on the determinants of COVID-19 vaccine-induced immunity and declining trend with time.