Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 157
Filtrar
2.
Cancer Epidemiol ; 87: 102495, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37992416

RESUMO

Physical activity is known to convey protection against several cancers. However, results on the risk of lymphoma overall and its subtypes have been inconsistent. The aim of this study was to investigate occupational and recreational physical activity in relation to risk of lymphoma subtypes adjusting for established occupational risk factors. We applied standardized tools to assess energy expenditure at work and in recreational physical activities to the questionnaire information on lifetime work and exercise history in 1117 lymphoma cases, including Hodgkin lymphoma, and B-cell (including chronic lymphocytic leukemia, and multiple myeloma) and T-cell non-Hodgkin's lymphoma (NHL) subtypes, and 1207 controls who took part in the multicentre European EpiLymph case-control study. We calculated the risk of lymphoma (all subtypes), B-cell NHL and its most represented subtypes, and Hodgkin's lymphoma (all subtypes) associated with weekly average Metabolic Equivalent of Task (MET-hours/week) and cumulative MET-hours of lifetime recreational, occupational, and total physical activity, with unconditional logistic regression and polytomous regression analysis adjusting by age, centre, sex, education, body mass index, history of farm work and solvent use. We observed an inverse association of occupational, and total physical activity with risk of lymphoma (all subtypes), and B-cell non-Hodgkin's lymphoma among women, and an upward trend in risk of Hodgkin's lymphoma with recreational and total physical activity among men, for which we cannot exclude chance or bias. Our results suggest no effect of overall physical activity on risk of lymphoma and its subtypes.


Assuntos
Doença de Hodgkin , Linfoma não Hodgkin , Linfoma , Masculino , Humanos , Feminino , Doença de Hodgkin/epidemiologia , Estudos de Casos e Controles , Linfoma/epidemiologia , Linfoma/etiologia , Fatores de Risco , Exercício Físico
4.
Front Immunol ; 13: 1040725, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389682

RESUMO

Respiratory tract infections (RTIs) are the most common infections in patients with rheumatic diseases under immunosuppressive treatment and may contribute to morbidity and mortality as well as increased healthcare costs. However, to date only limited data on infection risk in spondyloarthritis (SpA) patients are available. In this study we assessed the occurrence of respiratory tract infections in a monocentric real-world cohort consisting of 330 patients (168 psoriatic arthritis and 162 axial spondyloarthritis patients) and determined factors associated with increased infection risk. Out of 330 SpA patients, 89.3% had suffered from ≥ 1 upper respiratory tract infection (URTI) and 31.1% from ≥ 1 lower respiratory tract infection (LRTI) within the last two years. The most common URTIs were rhinitis and laryngitis/pharyngitis with 87.3% and 36.1%, respectively. Bronchitis constituted the most common LRTI, reported in 29.7% of patients. In a multivariate binomial logistic regression model occurrence of LRTI was associated with chronic lung disease (OR 17.44, p=0.006), glucocorticoid therapy (OR 9.24, p=0.012), previous history of severe airway infections (OR 6.82, p=0.013), and number of previous biological therapies (OR 1.72, p=0.017), whereas HLA B27 positivity was negatively associated (OR 0.29, p=0.025). Female patients reported significantly more LRTIs than male patients (p=0.006) and had a higher rate of antibiotic therapy (p=0.009). There were no significant differences between axSpA and PsA patients regarding infection frequency or antibiotic use. 45.4% of patients had required antibiotics for respiratory tract infections. Antibiotic therapy was associated with smoking (OR 3.40, p=0.008), biological therapy (OR 3.38, p=0.004), sleep quality (OR 1.13, p<0.001) and age (OR 0.96, p=0.030). Hypogammaglobulinemia (IgG<7g/l) was rare (3.4%) in this SpA cohort despite continuous immunomodulatory treatment. Awareness of these risk factors will assist physicians to identify patients with an increased infection risk, who will benefit from additional preventive measures, such as vaccination and smoking cessation or adjustment of DMARD therapy.


Assuntos
Artrite Psoriásica , Espondiloartrite Axial , Infecções Respiratórias , Espondilartrite , Humanos , Masculino , Feminino , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Infecções Respiratórias/tratamento farmacológico , Fatores de Risco , Espondilartrite/complicações , Espondilartrite/tratamento farmacológico , Espondilartrite/epidemiologia , Antibacterianos/uso terapêutico
5.
Leukemia ; 36(12): 2835-2844, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36273105

RESUMO

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10-8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10-9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10-8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.


Assuntos
Predisposição Genética para Doença , Linfoma não Hodgkin , Humanos , Estudo de Associação Genômica Ampla , Fatores de Risco , Linfoma não Hodgkin/genética , Células Germinativas , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único
6.
Cancer Epidemiol Biomarkers Prev ; 31(5): 1103-1110, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35244686

RESUMO

BACKGROUND: A previous International Lymphoma Epidemiology (InterLymph) Consortium evaluation of joint associations between five immune gene variants and autoimmune conditions reported interactions between B-cell response-mediated autoimmune conditions and the rs1800629 genotype on risk of B-cell non-Hodgkin lymphoma (NHL) subtypes. Here, we extend that evaluation using NHL subtype-specific polygenic risk scores (PRS) constructed from loci identified in genome-wide association studies of three common B-cell NHL subtypes. METHODS: In a pooled analysis of NHL cases and controls of Caucasian descent from 14 participating InterLymph studies, we evaluated joint associations between B-cell-mediated autoimmune conditions and tertile (T) of PRS for risk of diffuse large B-cell lymphoma (DLBCL; n = 1,914), follicular lymphoma (n = 1,733), and marginal zone lymphoma (MZL; n = 407), using unconditional logistic regression. RESULTS: We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR = 1.24; 95% confidence interval (CI), 1.08-1.43; T3 vs. T1: OR = 1.81; 95% CI, 1.59-2.07; P-trend (Ptrend) < 0.0001]. DLBCL risk also increased with increasing PRS tertile among those with an autoimmune condition, being highest for those with a B-cell-mediated autoimmune condition and a T3 PRS [OR = 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend < 0.0001, P-interaction (Pinteraction) = 0.49]. Follicular lymphoma and MZL risk demonstrated no evidence of joint associations or significant Pinteraction. CONCLUSIONS: Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions. IMPACT: Targeted genetic (PRS) screening among population subsets with autoimmune conditions may offer opportunities for identifying those at highest risk for (and early detection from) DLBCL.


Assuntos
Doenças Autoimunes , Linfoma Folicular , Linfoma Difuso de Grandes Células B , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Linfócitos B , Estudos de Casos e Controles , Estudo de Associação Genômica Ampla , Humanos , Linfoma Folicular/epidemiologia , Linfoma Folicular/genética , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/genética
7.
Blood ; 139(10): 1557-1563, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-34662377

RESUMO

Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL precursor state with a prevalence of up to 12% in aged individuals; however, the duration of MBL and the mechanisms of its evolution to CLL remain largely unknown. In this study, we sequenced the B-cell receptor (BcR) immunoglobulin heavy chain (IGH) gene repertoire of 124 patients with CLL and 118 matched controls in blood samples taken up to 22 years prior to diagnosis. Significant skewing in the BcR IGH gene repertoire was detected in the majority of patients, even before the occurrence of lymphocytosis and irrespective of the clonotypic IGH variable gene somatic hypermutation status. Furthermore, we identified dominant clonotypes belonging to major stereotyped subsets associated with poor prognosis up to 16 years before diagnosis in 14 patients with CLL. In 22 patients with longitudinal samples, the skewing of the BcR IGH gene repertoire increased significantly over time to diagnosis or remained stable at high levels. For 14 of 16 patients with available samples at diagnosis, the CLL clonotype was already present in the prediagnostic samples. Overall, our data indicate that the preclinical phase of CLL could be longer than previously thought, even in adverse-prognostic cases.


Assuntos
Leucemia Linfocítica Crônica de Células B , Linfocitose , Idoso , Linfócitos B , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Linfocitose/diagnóstico , Linfocitose/genética , Receptores de Antígenos de Linfócitos B/genética
8.
J Transl Genet Genom ; 5: 200-217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34622145

RESUMO

AIM: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk. METHODS: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis. RESULTS: We discovered positive associations between FROH and CLL (ß = 21.1, SE = 4.41, P = 1.6 × 10-6) and FL (ß = 11.4, SE = 5.82, P = 0.02) but not DLBCL (P = 1.0) or MZL (P = 0.91). For F3, we observed an association with CLL (ß = 27.5, SE = 6.51, P = 2.4 × 10-5). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity. CONCLUSION: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk.

9.
J Allergy Clin Immunol ; 148(5): 1332-1341.e5, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33895260

RESUMO

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations. OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts. METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered. RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years. CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.


Assuntos
Fatores Etários , Doenças Autoimunes/epidemiologia , Granuloma/epidemiologia , Infecções/epidemiologia , Transtornos Linfoproliferativos/epidemiologia , Doenças da Imunodeficiência Primária/epidemiologia , Sistema de Registros , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
10.
J Clin Immunol ; 41(6): 1250-1265, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33876323

RESUMO

PURPOSE: Common variable immune deficiency (CVID) confers an increased risk of lymphoid neoplasms, but reports describing the precise WHO specification of the lymphoma subtypes and their immunological environment are lacking. We therefore classified lymphomas-occurring in a cohort of 21 adult CVID patients during a 17-year period at our center-according to the 2016 WHO classification and characterized the local and systemic immunological context RESULTS: The median time between the onset of CVID and lymphoma was 14 years. Patients showed a high prevalence of preceding immune dysregulation: lymphadenopathy (n = 13, 62%), splenomegaly (n = 18, 86%), autoimmune cytopenia (n = 14, 67%), and gastrointestinal involvement (n = 15, 71%). The entities comprised extranodal marginal zone lymphoma (n = 6), diffuse large B cell lymphoma (n = 7), plasmablastic lymphoma (n = 1), classic Hodgkin lymphoma (n = 4, including three cases with germline CTLA4 mutations), T cell large granular lymphocytic leukemia (n = 2), and peripheral T cell lymphoma, not otherwise specified (n = 1), but no follicular lymphoma. An Epstein-Barr virus association was documented in eight of 16 investigated lymphomas. High expression of PDL1 by tumor cells in five and of PDL1 and PD1 by tumor-infiltrating macrophages and T cells in 12 of 12 investigated lymphomas suggested a tolerogenic immunological tumor environment. CONCLUSION: In summary, a diverse combination of specific factors like genetic background, chronic immune activation, viral trigger, and impaired immune surveillance contributes to the observed spectrum of lymphomas in CVID. In the future, targeted therapies, e.g., PD1/PDL1 inhibitors in CVID associated lymphomas with a tolerogenic environment may improve therapy outcome.


Assuntos
Imunodeficiência de Variável Comum/imunologia , Linfoma/imunologia , Adolescente , Adulto , Biomarcadores Tumorais/imunologia , Criança , Estudos de Coortes , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Herpesvirus Humano 4/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Adulto Jovem
11.
Cancer Epidemiol Biomarkers Prev ; 30(5): 874-885, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33619024

RESUMO

BACKGROUND: A growing body of evidence suggests that alterations of dietary fatty acid (FA) profiles are associated with colorectal cancer risk. However, data from large-scale epidemiologic studies using circulating FA measurements to objectively assess individual FA and FA categories are scarce. METHODS: We investigate the association between red blood cell (RBC) membrane FAs and risk of colorectal cancer in a case-control study nested within a large prospective cohort. After a median follow-up of 6.4 years, 1,069 incident colorectal cancer cases were identified and matched to 1,069 controls among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). The FA composition of RBC phospholipids (in mol%) was analyzed by gas chromatography, and their association with risk of colorectal cancer was estimated by multivariable adjusted conditional logistic regression models. RESULTS: After correction for multiple testing, subjects with higher concentrations of RBC stearic acid were at higher risk for colorectal cancer (OR = 1.23; 95% CI = 1.07-1.42, per 1 mol%). Conversely, colorectal cancer incidence decreased with increasing proportions of RBC n-3 PUFA, particularly eicosapentaenoic acid (0.75; 0.62-0.92, per 1 mol%). The findings for the n-6 PUFA arachidonic acid were inconsistent. CONCLUSIONS: The positive association between prediagnostic RBC stearic acid and colorectal cancer reflects putative differences in FA intake and metabolism between cancer cases and matched controls, which deserve further investigation. The inverse relationship between EPA and colorectal cancer is in line with the repeatedly reported protective effect of fish consumption on colorectal cancer risk. IMPACT: These findings add to the evidence on colorectal cancer prevention.


Assuntos
Neoplasias Colorretais/epidemiologia , Ácidos Graxos Insaturados/sangue , Ácidos Esteáricos/sangue , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Fatores de Risco
12.
Scand J Work Environ Health ; 47(1): 42-51, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33103203

RESUMO

Objectives This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts. Methods We explored the association in 1853 cases and 1997 controls who participated in the EpiLymph case-control study, conducted in six European countries in 1998-2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education. Results We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust [95% confidence interval (CI) 1.01-4.20]. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust [odd ratio (OR) 2.2, 95% CI 1.00-4.78], but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95-4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively). Conclusions Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma.


Assuntos
Linfoma , Doenças Profissionais , Exposição Ocupacional , Estudos de Casos e Controles , Poeira , Humanos , Linfoma/epidemiologia , Linfoma/etiologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Fatores de Risco
13.
Int J Cancer ; 148(9): 2115-2128, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33128820

RESUMO

To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.


Assuntos
Antropometria/métodos , Linfoma de Células B/epidemiologia , Estudos de Coortes , Expossoma , Feminino , Humanos , Estilo de Vida , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
15.
Cancer Med ; 9(22): 8412-8422, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32931637

RESUMO

BACKGROUND: Patients with cancer are considered a high-risk group for viral pneumonia, with an increased probability of fatal outcome. Here, we investigated the clinical characteristics and outcome of patients with solid and hematological cancers and concomitant Covid-19 at a Comprehensive Cancer Center in a Covid-19 hotspot area in Germany. METHODS: We performed a retrospective single center cohort study of 39 patients with hematological and solid cancers who were hospitalized at the University Hospital Freiburg for Covid-19. Using univariate and multivariate Cox regression models we compared time to severe events and overall survival to an age-matched control cohort of 39 patients with confirmed Covid-19 without a cancer diagnosis. RESULTS: In the cancer cohort 29 patients had a diagnosis of a solid tumor, and 10 had a hematological malignancy. In total, eight patients (21%) in the cancer and 14 patients (36%) from the noncancer cohort died during the observation period. Presence of a malignancy was not significantly associated with survival or time to occurrence of severe events. Major influences on mortality were high IL-6 levels at Covid-19 diagnosis (HR = 6.95, P = .0121) and age ≥ 65 years (HR = 6.22, P = .0156). CONCLUSIONS: Compared to an age-matched noncancer cohort, we did not observe an association between a cancer diagnosis and a more severe disease course or higher fatality rate in patients with Covid-19. Patients with a hematological malignancy showed a trend towards a longer duration until clinical improvement and longer hospitalization time compared to patients with a solid cancer. Cancer per se does not seem to be a confounder for dismal outcome in Covid-19.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Neoplasias Hematológicas/epidemiologia , Hospitalização/estatística & dados numéricos , Neoplasias/epidemiologia , Serviço Hospitalar de Oncologia/tendências , Pneumonia Viral/complicações , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Feminino , Alemanha/epidemiologia , Neoplasias Hematológicas/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/virologia , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Taxa de Sobrevida
16.
Sci Rep ; 10(1): 13814, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796953

RESUMO

Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case-control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.


Assuntos
Antígenos CD , Linfócitos B/imunologia , Índice de Massa Corporal , Quimiocina CXCL13 , Estilo de Vida , Linfoma Folicular/etiologia , Linfoma Difuso de Grandes Células B/etiologia , Biomarcadores , Estudos de Casos e Controles , Estudos de Coortes , Exercício Físico/fisiologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Ativação Linfocitária/imunologia , Linfoma Folicular/imunologia , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Estudos Prospectivos
17.
PLoS One ; 15(7): e0235658, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649712

RESUMO

Medical diagnostic X-rays are an important source of ionizing radiation (IR) exposure in the general population; however, it is unclear if the resulting low patient doses increase lymphoma risk. We examined the association between lifetime medical diagnostic X-ray dose and lymphoma risk, taking into account potential confounding factors, including medical history. The international Epilymph study (conducted in the Czech-Republic, France, Germany, Ireland, Italy, and Spain) collected self-reported information on common diagnostic X-ray procedures from 2,362 lymphoma cases and 2,465 frequency-matched (age, sex, country) controls. Individual lifetime cumulative bone marrow (BM) dose was estimated using time period-based dose estimates for different procedures and body parts. The association between categories of BM dose and lymphoma risk was examined using unconditional logistic regression models adjusting for matching factors, socioeconomic variables, and the presence of underlying medical conditions (atopic, autoimmune, infectious diseases, osteoarthritis, having had a sick childhood, and family history of lymphoma) as potential confounders of the association. Cumulative BM dose was low (median 2.25 mGy) and was not positively associated with lymphoma risk. Odds ratios (ORs) were consistently less than 1.0 in all dose categories compared to the reference category (less than 1 mGy). Results were similar after adjustment for potential confounding factors, when using different exposure scenarios, and in analyses by lymphoma subtype and by type of control (hospital-, population-based). Overall no increased risk of lymphoma was observed. The reduced ORs may be related to unmeasured confounding or other sources of systematic bias.We found little evidence that chronic medical conditions confound lymphoma risk and medical radiation associations.


Assuntos
Linfoma/etiologia , Exposição à Radiação/efeitos adversos , Radiação Ionizante , Adulto , Idoso , Medula Óssea/patologia , Medula Óssea/efeitos da radiação , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Linfoma/diagnóstico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doses de Radiação , Fatores de Risco
18.
Environ Health ; 19(1): 43, 2020 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334593

RESUMO

BACKGROUND: Evidence linking risk of lymphoma and B-cell lymphoma subtypes to ionizing radiation is inconclusive, particularly at low exposure levels. METHODS: We investigated risk of lymphoma (all subtypes), B-cell lymphomas, and its major subtypes, associated with low-level occupational exposure to ionizing radiation, in 2346 lymphoma cases and 2463 controls, who participated in the multicenter EpiLymph case-control study. We developed a job-exposure matrix to estimate exposure to ionizing radiation, distinguishing between internal and external radiation, and we applied it to the lifetime occupational history of study subjects, We calculated the Odds Ratio (OR) and its 95% confidence interval (95% CI) for lymphoma (all subtypes combined), B-cell lymphoma, and its major subtypes using unconditional, polytomous logistic regression adjusting for age, gender, and education. RESULTS: We did not observe an association between exposure metrics of external and internal radiation and risk of lymphoma (all subtypes), nor with B-cell lymphoma, or its major subtypes, at the levels regularly experienced in occupational settings. An elevated risk of diffuse large B cell lymphoma was observed among the most likely exposed study subjects with relatively higher exposure intensity, which would be worth further investigation. CONCLUSIONS: Further investigation is warranted on risk of B cell lymphoma subtypes associated with low-level occupational exposure to external ionizing radiation, and to clarify whether lymphoma should be included among the cancer outcomes related to ionizing radiation.


Assuntos
Linfoma/epidemiologia , Exposição Ocupacional/efeitos adversos , Radiação Ionizante , Adulto , Idoso , Estudos de Casos e Controles , República Tcheca/epidemiologia , Feminino , França/epidemiologia , Alemanha/epidemiologia , Humanos , Irlanda/epidemiologia , Itália/epidemiologia , Linfoma/etiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Espanha/epidemiologia
20.
Artigo em Alemão | MEDLINE | ID: mdl-32185449

RESUMO

BACKGROUND: Infectious diseases continue to play an important role for disease perception, health-economic considerations and public health in Germany. In recent years, infectious diseases have been linked to the development of non-communicable diseases. Analyses of the German National Cohort (GNC) may provide deeper insights into this issue and pave the way for new targeted approaches in disease prevention. OBJECTIVES: The aim was to describe the tools used to assess infectious diseases and to present initial data on infectious disease frequencies, as well as to relate the GNC assessment tools to data collection methods in other studies in Germany. METHODS: As part of the baseline examination, questions regarding infectious diseases were administered using both an interview and a self-administered touchscreen questionnaire. Data from the initial 101,787 GNC participants were analysed. RESULTS: In the interview, 0.2% (HIV/AIDS) to 8.6% (shingles) of respondents reported ever having a medical diagnosis of shingles, postherpetic neuralgia (in cases where shingles was reported), hepatitis B/C, HIV/AIDS, tuberculosis or sepsis if treated in hospital. In the questionnaire, 12% (cystitis) to 81% (upper respiratory tract infections) of respondents reported having experienced at least one occurrence of upper or lower respiratory tract infections, gastrointestinal infections, cystitis or fever within the past 12 months. OUTLOOK: The cross-sectional analyses of data and tools presented here - for example on determinants of susceptibility to self-reported infections - can be anticipated from the year 2021 onward. Beyond that, more extensive research into infectious disease epidemiology will follow, particularly once analyses of GNC biological materials have been performed.


Assuntos
Doenças Transmissíveis/epidemiologia , Estudos de Coortes , Estudos Transversais , Alemanha/epidemiologia , Humanos , Autorrelato , Inquéritos e Questionários
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA