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1.
Genet Epidemiol ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31407831

RESUMO

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

2.
Aliment Pharmacol Ther ; 50(6): 654-663, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31347731

RESUMO

BACKGROUND: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease, and most available data on gastric MALT lymphoma (GML) come from clinical studies of selected patients treated in centres of excellence. AIMS: To analyse the clinical features, management and survival of GML patients in a population-based study in France METHODS: All new cases of GML diagnosed between 2002 and 2010 in 11 French areas covered by cancer registries were included. Pathology reports were verified and, if necessary, reviewed by an expert pathologist. All clinical data were retrospectively collected from medical files and analysed using stata V. 14 software. RESULTS: Four hundred and sixteen patients with confirmed GML (50% male, median age 67 years) were identified. Among them, 44 showed an early transformation into diffuse large B cell lymphoma and were considered to have had an initially missed high-grade lymphoma. At diagnosis, 76% of patients were at stage IE/II, and 24% at stage III/IV of the disease. Helicobacter pylori infection was found in 57% of the patients. Eradication treatment was administered to 76% of patients and complete remission (CR) was obtained in 39%. One hundred and ninety patients received at least one other treatment, including 10 already in CR after eradication. Altogether, CR was obtained in 70% of patients and the 5-year overall survival was 79% (95% CI [75-83]). CONCLUSIONS: In comparison to clinical series, in the general population, GMLs are more frequently diagnosed at an advanced stage, their clinical management is heterogeneous, and there is a risk of misdiagnosis and overtreatment. These results highlight the necessity of following currently available guidelines in this field.

5.
Nat Commun ; 9(1): 4182, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305637

RESUMO

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P = 1.36 × 10-54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10-19). Both risk alleles are observed at a low frequency among controls (~2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.

6.
Cancer Res ; 78(14): 4086-4096, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29735552

RESUMO

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086-96. ©2018 AACR.

7.
Blood ; 131(23): 2541-2551, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29674426

RESUMO

Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; P = 4.4 × 10-94). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P = 7.8 × 10-30) and observed high discrimination (c-statistic = 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; P = 9.8 × 10-16). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH. The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL.

9.
J Cancer Res Clin Oncol ; 144(4): 629-635, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29022078

RESUMO

PURPOSE: Mantle cell lymphoma (MCL) is a rare non-Hodgkin's lymphoma entity with a poor prognosis. Therapeutic advances have improved the survival of patients enrolled in clinical trials; however, their impact on patients outside clinical trials remains unclear. In this work, we compared patient outcome inside and outside clinical trials. METHODS: We identified MCL patients recorded in six French population-based registries between 2008 and 2012 to perform a comparison with patients enrolled in two prospective multicenter MCL clinical trials conducted by the LYSA group during the same period. Variables associated with inclusion in a clinical trial were identified using a logistic regression. Pohar-Perme estimator and Nelson et al. flexible parametric model was used to estimate net survival probabilities and prognosis factors on excess mortality. RESULTS: A total of 312 registry patients were compared to the 372 patients enrolled in LYSA clinical trials. Patients included in clinical trials were younger (median age 60 vs 74, p < 0.001). Age and Ann Arbor stage IV were independently associated with enrollment [OR = 0.09 (0.06-0.12) and OR = 1.61 (1.11-2.34), respectively]. The 4 year net survival was better in clinical trials [79.9% (75.9-84.7) vs 60.3% (53.6-67.0)]. This result was confirmed in multivariate analysis in patients older than 65 years with a lower excess mortality rate [0.33 (0.17-0.66)]. CONCLUSIONS: MCL included in trials are highly selected patients who are not representative of MCL patients who are encountered in everyday practice. With widened inclusion criteria, clinical trial patients could be more representative of the general population.


Assuntos
Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/mortalidade , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Casos e Controles , Feminino , França/epidemiologia , Humanos , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sistema de Registros
10.
Hematol Oncol ; 36(2): 422-428, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29218734

RESUMO

The assessment of minimal residual disease (MRD) in acute myeloblastic leukemia is of growing interest as a prognostic marker of patients' outcome. Multiparameter flow cytometry (MFC), tracking leukemia-associated immunophenotypic patterns, has been shown in several studies to be a useful tool to investigate MRD. Here, we report a multicenter prospective study which allowed to define a harmonized analysis strategy, as well as the efficacy of MFC MRD to predict outcome. This study included 276 patients, in 10 different MFC centers, of whom 268 had at least 1 MRD check point. The combination of a CD45, CD34, and CD33 backbone, with the addition of CD117, CD13, CD7, and CD15 in 2 five-color tubes allowed to define each patient's multiparameter immunophenotypic characteristics at diagnosis, according to a Boolean combination of gates. The same individual diagnosis gating strategy was then applied at each MRD time point for each patient. MRD levels were stratified according to log by log thresholds, from 5 × 10-2 (the classical morphological threshold to define remission) down to <5 × 10-5 . MRD was found to be constantly negative (<5 × 10-5 ) for 148 patients. Survival analyses significantly associated MRD negativity with a good prognosis and any positive value with poorer outcome. All P values were <0.0001 both for disease-free and overall survival at the earliest time point (post-induction, MRD1) as well as when considering all time points together. Finally, MRD levels were independent of cytogenetics and allowed in fact to further stratify all cytogenetics risk groups. In summary, this multicenter study demonstrates that a simple combination of immunophenotypic markers successfully allows for the detection of MRD in acute myeloblastic leukemia patients, with a strong correlation to outcome.


Assuntos
Citometria de Fluxo/métodos , Leucemia Mieloide Aguda/diagnóstico , Neoplasia Residual/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Imunofenotipagem , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto Jovem
11.
J Clin Oncol ; 35(18): 2008-2017, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28459613

RESUMO

Purpose To prospectively assess the clinical impact of expert review of lymphoma diagnosis in France. Materials and Methods From January 2010 to December 2013, 42,145 samples from patients with newly diagnosed or suspected lymphomas were reviewed, according to the 2008 WHO classification, in real time by experts through the Lymphopath Network. Changes in diagnosis between referral and expert review were classified as major or minor according to their potential impact on patient care. Results The 42,145 reviewed samples comprised 36,920 newly diagnosed mature lymphomas, 321 precursor lymphoid neoplasms, 314 myeloid disorders, and 200 nonhematopoietic neoplasms, with 4,390 benign lesions. There were 4,352 cutaneous and 32,568 noncutaneous lymphomas. The most common mature noncutaneous lymphomas were diffuse large B-cell lymphomas (32.4%), follicular lymphomas (15.3%), classic Hodgkin lymphomas (13%), peripheral T-cell lymphomas (6.3%) of which angioimmunoblastic T-cell lymphomas (2.3%) were the most frequent, and mucosa-associated lymphoid tissue lymphomas (5.8%). A diagnostic change between referral and expert review occurred in 19.7% of patients, with an estimated impact on patient care for 17.4% of patients. This rate was significantly higher for patients sent with a provisional diagnosis seeking expert second opinion (37.8%) than for patients sent with a formal diagnosis (3.7%). The most frequent discrepancies were misclassifications in lymphoma subtype (41.3%), with 12.3% being misclassifications among small B-cell lymphoma entities. Fewer than 2% of changes were between benign and malignant lymphoid conditions. Minor changes (2.3%) mostly consisted of follicular lymphoma misgrading and diffuse large B-cell lymphoma subtype misclassification. Conclusion To our knowledge, this study provides the largest ever description of the distribution of lymphoma entities in a western country and highlights how expert review significantly contributes to a precise lymphoma diagnosis and optimal clinical management in a proportion of patients.


Assuntos
Competência Clínica , Linfoma/diagnóstico , Linfoma/patologia , Patologia Clínica , França , Humanos , Linfoma/classificação , Linfoma/terapia , Gradação de Tumores , Estudos Prospectivos , Encaminhamento e Consulta
12.
Cytometry B Clin Cytom ; 92(6): 498-507, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28321976

RESUMO

OBJECTIVES: Microscopic leukocyte differentials display many drawbacks. Several single 5 to 8-color tubes using multiparameter flow cytometry (MFC) are able to provide extended differentials with sequential gating-based analysis strategies. We investigated a new 5-color MFC method to perform an extended 8-part differential with a simplified gating strategy. METHODS: Whole blood was stained with a combination of antibodies including HLA-DR-FITC/CD19-PE/CD45-ECD/CD16-PC5 + CD71-PC5/CD5-PC7. RESULTS: An original approach was developed to exclude debris and straightforwardly gate the cells to identify sixteen populations. Strong correlations were obtained with the analyzer for neutrophils, lymphocytes, monocytes, and eosinophils (R2 >0.9). Abnormal cells, such as immature granulocytes and blast cells were identified with a good sensitivity and excellent correlation against cytomorphologic review (R2 =0.66 and 0.99, respectively). The choice of HLA-DR and CD5 improved specificity for the identification of activated T-lymphocytes and some lymphoid neoplastic cells, respectively. CONCLUSIONS: Here a new cytometric differential is proposed with a robust gating strategy which may be used even by unskilled cytometrists and can be easily automated. © 2017 International Clinical Cytometry Society.


Assuntos
Anticorpos/química , Citometria de Fluxo/métodos , Corantes Fluorescentes/química , Imunofenotipagem/métodos , Leucócitos/classificação , Anticorpos/metabolismo , Especificidade de Anticorpos , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos CD19/imunologia , Antígenos CD19/metabolismo , Biomarcadores/metabolismo , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Expressão Gênica , Antígenos HLA-DR/imunologia , Antígenos HLA-DR/metabolismo , Humanos , Leucemia/diagnóstico , Leucemia/imunologia , Leucemia/patologia , Antígenos Comuns de Leucócito/imunologia , Antígenos Comuns de Leucócito/metabolismo , Contagem de Leucócitos , Leucócitos/imunologia , Leucócitos/patologia , Linfoma/diagnóstico , Linfoma/imunologia , Linfoma/patologia , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/imunologia , Síndromes Mielodisplásicas/patologia , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Receptores da Transferrina/imunologia , Receptores da Transferrina/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
Leuk Lymphoma ; 58(6): 1366-1375, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28271952

RESUMO

This prospective non-interventional study assessed the management of relapsed/refractory CLL after one or two treatments with rituximab, and retreatment with a rituximab-based regimen. An interim analysis was performed at the end of the induction period in 192 evaluable patients. Median age was 72 years [35-89], first relapse (55%), and second relapse (45%). Rituximab administered during first (68%), second (92%), or both treatment lines (20%). R-bendamustine administered in 56% of patients, R-purine analogs (21%), and R-alkylating agents (19%). The overall response rate (ORR) was 74.6%, in favor of R-purine analogs (90%), R-bendamustine (75%), and R-alkylating agents (69%). Lower ORR in Del 17p patients (43%) and third time rituximab (31%). Most frequent adverse events were hematological (23% patients) including neutropenia (11%) and infections (12%); grade 3/4 AEs (23% patients), mainly hematological (18%); death during induction treatment (7%). This first large study focusing on relapsed/refractory CLL patients retreated with rituximab-based regimens is still ongoing.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Rituximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , França/epidemiologia , Humanos , Leucemia Linfocítica Crônica de Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Recidiva , Retratamento , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Resultado do Tratamento
14.
Cancer Epidemiol Biomarkers Prev ; 26(6): 876-885, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28223430

RESUMO

Background: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case-control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI.Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls.Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04-1.14; P = 0.007]. We observed significant heterogeneity by study design (P = 0.04), noting the BMI-multiple myeloma association only for population-based studies (Ptrend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m2; OR, 1.2; 95% CI, 1.1-1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI (Pinteraction <0.0001); we noted statistically significant associations with multiple myeloma for persons overweight (25-<30 kg/m2) or obese (30+ kg/m2) in both younger and usual adulthood (vs. individuals consistently <25 kg/m2), but not for those overweight or obese at only one time period.Conclusions: BMI-associated increases in multiple myeloma risk were highest for individuals who were overweight or obese throughout adulthood.Impact: These findings provide the strongest evidence to date that earlier and later adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876-85. ©2017 AACR.


Assuntos
Antropometria/métodos , Índice de Massa Corporal , Mieloma Múltiplo/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Fatores de Risco
15.
Acta Derm Venereol ; 97(3): 358-364, 2017 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-27722764

RESUMO

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare condition usually considered to have a favourable prognosis. However, it is not known whether polychemotherapy or immunosuppressive-based therapy is the best approach for treating SPTCL. Using data collected between 2000 and 2012 in France, we analysed clinical, biological and pathological data of 27 patients with SPTCL. Medical history revealed that 40% of patients had been previously diagnosed with an autoimmune disorder and 22% with inflammatory panniculitis. Haemophagocytic syndrome was present in 37% of cases. Autoantibodies were positive in 65% of cases. Complete remission (CR) was reached in 74% of cases. Immunosuppressive drug treatment was given in 69.5% of patients (group 1) and polychemotherapy in 30.5% (group 2). CR was 81.2% and 28.5% (p?=?0.025), respectively. Progression rate was 6.2% and 42.8% (p?=?0.067), respectively. This study suggests that immunosuppressive drugs should be considered as the first-line treatment for SPTCL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunossupressores/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Paniculite/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biópsia , Criança , Pré-Escolar , Progressão da Doença , Feminino , França , Humanos , Imunossupressores/efeitos adversos , Lactente , Linfoma de Células T/imunologia , Linfoma de Células T/mortalidade , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Paniculite/imunologia , Paniculite/mortalidade , Paniculite/patologia , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Haematologica ; 102(3): 584-592, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27909221

RESUMO

The survival of patients with diffuse large B-cell lymphoma has increased during the last decade as a result of addition of anti-CD20 to anthracycline-based chemotherapy. Although the trend is encouraging, there are persistent differences in survival within and between the USA and European countries suggesting that non-biological factors play a role. Our aim was to investigate the influence of such factors on relative survival of patients with diffuse large B-cell lymphoma. We conducted a retrospective, multicenter, registry-based study in France on 1165 incident cases of diffuse large B-cell lymphoma between 2002 and 2008. Relative survival analyses were performed and missing data were controlled with the multiple imputation method. In a multivariate analysis, adjusted for age, sex and International Prognostic Index, we confirmed that time period was associated with a better 5-year relative survival. The registry area, the medical specialty of the care department (onco-hematology versus other), the time to travel to the nearest teaching hospital, the place of treatment (teaching versus not-teaching hospital -borderline significance), a comorbidity burden and marital status were independently associated with the 5-year relative survival. Adjusted for first-course treatment, inclusion in a clinical trial and treatment discussion in a multidisciplinary meeting were strongly associated with a better survival outcome. In contrast, socio-economic status (determined using the European Deprivation Index) was not associated with outcome. Despite therapeutic advances, various non-biological factors affected the relative survival of patients with diffuse large B-cell lymphoma. The notion of lymphoma-specific expertise seems to be essential to achieve optimal care management and reopens the debate regarding centralization of these patients' care in hematology/oncology departments.


Assuntos
Linfoma Difuso de Grandes Células B/mortalidade , Vigilância da População , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Comorbidade , Análise Fatorial , Feminino , França/epidemiologia , Humanos , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Prognóstico , Sistema de Registros , Classe Social , Análise de Sobrevida , Adulto Jovem
17.
Int J Cancer ; 139(5): 1073-80, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27130333

RESUMO

Pancreatic survival is one of the worst in oncology. To what extent wait times affect outcomes in unknown No population-based study has previously explored patient and treatment delays among individuals with pancreatic cancer. The aim of this study was to estimate patient and treatment delays in patients with pancreatic cancer and to measure their association with survival in a nonselected population. All patients diagnosed with pancreatic cancer for the first time between 2009 and 2011 and registered in two French digestive cancer registries were included. Patient delay (time from onset of symptoms until the first consultation categorized into <1 or ≥1 month), and treatment delay (time between the first consultation and treatment categorized into less or more than 29 days, the median time) were collected. Overall delay was used to test associations between survival and the timeliness of care by combining patient delay and treatment delay. Patient delay was longer than 1 month in 46% of patients. A patient delay longer than one month was associated with the absence of jaundice (p < 0.001) and the presence of metastasis (p = 0.003). After adjusting for other covariates, such as symptoms and treatment, the presence of metastasis was negatively associated with treatment delay longer than 29 days (p = 0.025). After adjustment for other covariates, especially metastatic dissemination and the result of the resection, overall delay was not significantly associated with prognosis. We found little evidence to suggest that timely care was associated with the survival of patients.


Assuntos
Neoplasias Pancreáticas/epidemiologia , Tempo para o Tratamento , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Diagnóstico Tardio , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Vigilância da População , Fatores de Risco , Taxa de Sobrevida
18.
Int J Epidemiol ; 45(3): 728-40, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26971321

RESUMO

BACKGROUND: Based on epidemiological commonalities, multiple sclerosis (MS) and Hodgkin lymphoma (HL), two clinically distinct conditions, have long been suspected to be aetiologically related. MS and HL occur in roughly the same age groups, both are associated with Epstein-Barr virus infection and ultraviolet (UV) light exposure, and they cluster mutually in families (though not in individuals). We speculated if in addition to sharing environmental risk factors, MS and HL were also genetically related. Using data from genome-wide association studies (GWAS) of 1816 HL patients, 9772 MS patients and 25 255 controls, we therefore investigated the genetic overlap between the two diseases. METHODS: From among a common denominator of 404 K single nucleotide polymorphisms (SNPs) studied, we identified SNPs and human leukocyte antigen (HLA) alleles independently associated with both diseases. Next, we assessed the cumulative genome-wide effect of MS-associated SNPs on HL and of HL-associated SNPs on MS. To provide an interpretational frame of reference, we used data from published GWAS to create a genetic network of diseases within which we analysed proximity of HL and MS to autoimmune diseases and haematological and non-haematological malignancies. RESULTS: SNP analyses revealed genome-wide overlap between HL and MS, most prominently in the HLA region. Polygenic HL risk scores explained 4.44% of HL risk (Nagelkerke R(2)), but also 2.36% of MS risk. Conversely, polygenic MS risk scores explained 8.08% of MS risk and 1.94% of HL risk. In the genetic disease network, HL was closer to autoimmune diseases than to solid cancers. CONCLUSIONS: HL displays considerable genetic overlap with MS and other autoimmune diseases.


Assuntos
Estudo de Associação Genômica Ampla , Doença de Hodgkin/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único , Feminino , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Modelos Lineares , Masculino
19.
Cancer Epidemiol Biomarkers Prev ; 25(1): 217-21, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26464426

RESUMO

BACKGROUND: Female sex hormones are known to have immunomodulatory effects. Therefore, reproductive factors and exogenous hormone use could influence the risk of multiple myeloma in women. However, the role of hormonal factors in multiple myeloma etiology remains unclear because previous investigations were underpowered to detect modest associations. METHODS: We conducted a pooled analysis of seven case-control studies included in the International Multiple Myeloma Consortium, with individual data on reproductive factors and exogenous hormone use from 1,072 female cases and 3,541 female controls. Study-specific odds ratios and corresponding 95% confidence intervals (CI) were estimated using logistic regression and pooled analyses were conducted using random effects meta-analyses. RESULTS: Multiple myeloma was not associated with reproductive factors, including ever parous [OR = 0.92; 95% confidence interval (CI), 0.68-1.25], or with hormonal contraception use (OR = 1.04; 95% CI, 0.80-1.36). Postmenopausal hormone therapy users had nonsignificantly reduced risks of multiple myeloma compared with never users, but this association differed across centers (OR = 0.65; 95% CI, 0.37-1.15, I(2) = 76.0%, Pheterogeneity = 0.01). CONCLUSIONS: These data do not support a role for reproductive factors or exogenous hormones in myelomagenesis. IMPACT: Incidence rates of multiple myeloma are higher in men than in women, and sex hormones could influence this pattern. Associations with reproductive factors and exogenous hormone use were inconclusive despite our large sample size, suggesting that female sex hormones may not play a significant role in multiple myeloma etiology.


Assuntos
Terapia de Reposição Hormonal/efeitos adversos , Mieloma Múltiplo/etiologia , Pós-Menopausa , História Reprodutiva , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Adulto Jovem
20.
Environ Health Perspect ; 124(4): 396-405, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26340796

RESUMO

BACKGROUND: Various occupations have been associated with an elevated risk of non-Hodgkin lymphoma (NHL), but results have been inconsistent across studies. OBJECTIVES: We investigated occupational risk of NHL and of four common NHL subtypes with particular focus on occupations of a priori interest. METHODS: We conducted a pooled analysis of 10,046 cases and 12,025 controls from 10 NHL studies participating in the InterLymph Consortium. We harmonized the occupational coding using the 1968 International Standard Classification of Occupations (ISCO-1968) and grouped occupations previously associated with NHL into 25 a priori groups. Odds ratios (ORs) adjusted for center, age, and sex were determined for NHL overall and for the following four subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and peripheral T-cell lymphoma (PTCL). RESULTS: We confirmed previously reported positive associations between NHL and farming occupations [field crop/vegetable farm workers OR = 1.26; 95% confidence interval (CI): 1.05, 1.51; general farm workers OR = 1.19; 95% CI: 1.03, 1.37]; we also confirmed associations of NHL with specific occupations such as women's hairdressers (OR = 1.34; 95% CI: 1.02, 1.74), charworkers/cleaners (OR = 1.17; 95% CI: 1.01, 1.36), spray-painters (OR = 2.07; 95% CI: 1.30, 3.29), electrical wiremen (OR = 1.24; 95% CI: 1.00, 1.54), and carpenters (OR = 1.42; 95% CI: 1.04, 1.93). We observed subtype-specific associations for DLBCL and CLL/SLL in women's hairdressers and for DLBCL and PTCL in textile workers. CONCLUSIONS: Our pooled analysis of 10 international studies adds to evidence suggesting that farming, hairdressing, and textile industry-related exposures may contribute to NHL risk. Associations with women's hairdresser and textile occupations may be specific for certain NHL subtypes. CITATION: 't Mannetje A, De Roos AJ, Boffetta P, Vermeulen R, Benke G, Fritschi L, Brennan P, Foretova L, Maynadié M, Becker N, Nieters A, Staines A, Campagna M, Chiu B, Clavel J, de Sanjose S, Hartge P, Holly EA, Bracci P, Linet MS, Monnereau A, Orsi L, Purdue MP, Rothman N, Lan Q, Kane E, Seniori Costantini A, Miligi L, Spinelli JJ, Zheng T, Cocco P, Kricker A. 2016. Occupation and risk of non-Hodgkin lymphoma and its subtypes: a pooled analysis from the InterLymph Consortium. Environ Health Perspect 124:396-405; http://dx.doi.org/10.1289/ehp.1409294.


Assuntos
Linfoma não Hodgkin/epidemiologia , Doenças Profissionais/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Agricultura , Barbearia , Estudos de Casos e Controles , Feminino , Humanos , Linfoma não Hodgkin/etiologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Fatores de Risco , Indústria Têxtil
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