ABSTRACT
Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.
Subject(s)
Pancreatic Neoplasms/epidemiology , Smoking/adverse effects , Adult , Aged , Case-Control Studies , Cohort Studies , Diabetes Mellitus/epidemiology , Europe/epidemiology , Female , Humans , Logistic Models , Male , Medical History Taking , Middle Aged , Neoplasms/epidemiology , Pancreatic Neoplasms/genetics , Risk Assessment , Risk FactorsABSTRACT
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.
Subject(s)
Carcinoma, Pancreatic Ductal/epidemiology , Computational Biology , Pancreatic Neoplasms/epidemiology , Systems Analysis , Systems Biology , Biomarkers, Tumor/genetics , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/genetics , Case-Control Studies , Cluster Analysis , Comorbidity , Databases, Genetic , Europe/epidemiology , Factor Analysis, Statistical , Humans , Logistic Models , Multivariate Analysis , Odds Ratio , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Principal Component Analysis , Risk Assessment , Risk Factors , Time FactorsABSTRACT
BACKGROUND: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. OBJECTIVE: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. METHODS: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. RESULTS: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. CONCLUSION & CLINICAL RELEVANCE: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.
Subject(s)
Asthma/blood , Asthma/genetics , Immunoglobulin E/blood , Rhinitis, Allergic, Seasonal/blood , Rhinitis, Allergic, Seasonal/genetics , Adult , Asthma/epidemiology , Biomarkers/blood , Female , Follow-Up Studies , Humans , Male , Rhinitis, Allergic, Seasonal/epidemiologyABSTRACT
INTRODUCTION AND METHODS: The EGEA study (epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), which combines a case-control and a family-based study of asthma case (n=2120 subjects) with three surveys over 20 years, aims to identify environmental and genetic factors associated with asthma and asthma-related phenotypes. We summarize the results of the phenotypic characterization and the investigation of environmental and genetic factors of asthma and asthma-related phenotypes obtained since 2007 in the EGEA study (42 articles). RESULTS: Both epidemiological and genetic results confirm the heterogeneity of asthma. These results strengthen the role of the age of disease onset, the allergic status and the level of disease activity in the identification of the different phenotypes of asthma. The deleterious role of active smoking, exposure to air pollution, occupational asthmogenic agents and cleaning products on the prevalence and/or activity of asthma has been confirmed. Accounting for gene-environment interactions allowed the identification of new genetic factors underlying asthma and asthma-related traits and better understanding of their mode of action. CONCLUSION: The EGEA study is contributing to the advances in respiratory research at the international level. The new phenotypic, environmental and biological data available in EGEA study will help characterizing the long-term evolution of asthma and the factors associated to this evolution.
Subject(s)
Asthma/etiology , Bronchial Hyperreactivity/etiology , Gene-Environment Interaction , Hypersensitivity, Immediate/etiology , Adolescent , Adult , Aged , Air Pollution/adverse effects , Asthma/epidemiology , Asthma/genetics , Bronchial Hyperreactivity/epidemiology , Bronchial Hyperreactivity/genetics , Case-Control Studies , Child , Environmental Exposure , Family Health , France , Genetic Association Studies , Genetic Heterogeneity , Genetic Predisposition to Disease , Health Surveys , Humans , Hypersensitivity, Immediate/epidemiology , Hypersensitivity, Immediate/genetics , Male , Middle Aged , Occupational Exposure , Phenotype , Polymorphism, Single Nucleotide , Risk Factors , Smoking/adverse effects , Tobacco Smoke Pollution/adverse effectsABSTRACT
The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern. The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010. The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20-44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991-1993; n = 6,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998-2000; n = 18,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007-2010; n = 10,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time. From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19-1.59) from 1998-2000 to 2007-2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991. The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhinitis.
Subject(s)
Asthma/epidemiology , Rhinitis, Allergic, Perennial/epidemiology , Rhinitis, Allergic, Seasonal/epidemiology , Adult , Cross-Sectional Studies , Female , Humans , Italy/epidemiology , Male , Prevalence , Respiratory Sounds , Smoking/epidemiology , Surveys and Questionnaires , Young AdultABSTRACT
The aim of this study is to find and test a predictive model that could be suitable to estimate the outdoor NO(2) concentrations at individual level, by integrating ecological measurements recorded by local monitoring stations with individual information collected by a questionnaire. For this purpose, the data from the Italian centres of the European Community Respiratory Health Survey II (ECRHS II) has been used. Outdoor NO(2) concentrations were measured using NO(2) passive sampling tubes (PS-NO(2)), exposed outdoor for 14 days, between January 2001 and January 2003. Simultaneously, average NO(2) concentrations were collected from all the monitoring stations of the three centres (MS-NO(2)). Individual measurements carried out with passive samplers were compared with the corresponding NO(2) 2-week concentrations obtained as the average of all local (background and traffic) monitoring stations (MS-NO(2)). A multiple linear regression model was fitted to the data using the 2-week PS-NO(2) concentrations as the response variable and questionnaire information and MS-NO(2) concentrations as predictors. The model minimizing the root mean square error (RMSE), obtained from a ten-fold cross validation, was selected. The model with the best predictive ability included centre, season of the survey, MS-NO(2) concentrations, type and age of building, residential area and reported intensity of heavy-duty traffic and explained the 68.9% of the variance. The non-parametric correlation between PS-NO(2) and the concentrations estimated by the model is 0.81 (95% CI: 0.77-0.85). This study shows that over short periods (2 weeks) a good prediction of home outdoor exposure to NO(2) can be achieved by simply combining routinely collected ecological data with dwelling characteristics and self-reported intensity of heavy traffic. Further studies are needed to extend this prediction to long-term exposure.
Subject(s)
Air Pollutants/analysis , Environmental Monitoring , Models, Chemical , Nitrogen Dioxide/analysis , Humans , Italy , Linear Models , Vehicle Emissions/analysisABSTRACT
In order to establish whether or not here is an association between cancer and intense growth of seborrheic keratosis, the so-called Leser-Trelat sign, we conducted a case control study in which the number and features of seborrheic keratosis in 82 patients with recent solid tumours, were compared with 82 age- and sex-matched controls. Neither numbers nor features of seborrheic keratosis differed significantly in patients and controls. Eruptive seborrheic keratosis was noted in only one patient and one control. This study showed that solid malignancies are not generally associated with an increase in the number or size of seborrheic keratosis lesions, thus suggesting that they are not controlled by a hypothetical secretion of growth factors by tumours. Our results suggest that Leser-Trelat is either a coincidence, or at most a very rare sign of unusual types of cancer. We also showed that multiple cherry angiomas, previously reported to be a paraneoplastic sign, are not regularly associated with solid tumours.
Subject(s)
Keratosis/pathology , Paraneoplastic Syndromes/pathology , Adult , Aged , Case-Control Studies , Dermatitis, Seborrheic/pathology , Female , Humans , Male , Middle AgedABSTRACT
Se analizan los aspectos etiologicos, clinicos, histopatologicos y de ultraestructura de 3 casos de HEF ocurridos en ninos de una misma familia. La presencia de papulas en la mucosa labial y bucal asociada a un cuadro histologico de acantosis, paraqueratosis y papilomatosis con elongacion de las crestas papilares junto con la aparicion de celulas de citoplasma claro, fusiformes y nucleos hipercromaticos en la epidermis, reune los requisitos para el diagnostico de Enfermedad de Heck. El hallazgo de inclusiones nucleares observadas en microscopia electronica, compatibles con virus del tipo Papova, favorece la posibilidad de una etiologia viral
Subject(s)
Mouth Diseases , Mouth Mucosa , Papillomaviridae , Hyperplasia , WartsABSTRACT
Se analizan los aspectos etiologicos, clinicos, histopatologicos y de ultraestructura de 3 casos de HEF ocurridos en ninos de una misma familia. La presencia de papulas en la mucosa labial y bucal asociada a un cuadro histologico de acantosis, paraqueratosis y papilomatosis con elongacion de las crestas papilares junto con la aparicion de celulas de citoplasma claro, fusiformes y nucleos hipercromaticos en la epidermis, reune los requisitos para el diagnostico de Enfermedad de Heck. El hallazgo de inclusiones nucleares observadas en microscopia electronica, compatibles con virus del tipo Papova, favorece la posibilidad de una etiologia viral