Incidence et caractéristiques des hémopathies malignes au cours de l’artérite à cellules géantes

Introduction L’arterite a cellules geantes (ACG) est une vascularite du sujet âge au cours de laquelle les cellules mononucleees jouent un role physiopathologique majeur. L’hematopoiese clonale est un phenomene dont la frequence augmente egalement avec l’âge et qui conduit a l’apparition de mutations responsables de la survenue d’hemopathies malignes (HM) ou de mutations des cellules effectrices de l’immunite responsables de pathologies inflammatoires. Notre hypothese est qu’il existe une association specifique entre certaines HM et l’ACG. Nous avons pu etudier cette hypothese en croisant les donnees du registre des hemopathies de Cote d’Or (RHEMCO) et celles de tous les laboratoires d’anat…

Étude des cancers secondaires dans les lymphomes non hodgkiniens au sein d’un registre : impact du rituximab

Introduction Le nombre de survivants d’un lymphome folliculaire (LF) ou d’un lymphome B diffus a grandes cellules (LBDGC) est en augmentation. L’etude des cancers secondaires est un enjeu important de sante publique. Le risque lie a la chimiotherapie conventionnelle est bien decrit, mais peu de donnees existent pour le rituximab. Methode Etude retrospective au sein du Registre des hemopathies malignes de Cote d’or (RHEMCO) comparant l’incidence des cancers secondaires avant/apres l’introduction du rituximab, chez les patients ayant un LF ou un LBDGC diagnostique entre 1990 et 2010. La comparaison du taux de cancers secondaires observe au taux attendu dans la population francaise a ete expri…

Etiologic Heterogeneity Among Non-Hodgkin Lymphoma Subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy and the fifth most common type of cancer in more developed regions of the world (1). Numerous NHL subtypes with distinct combinations of morphologic, immunophenotypic, genetic, and clinical features are currently recognized (2,3). The incidence of NHL subtypes varies substantially by age, sex, and race/ethnicity (4–7). However, the etiological implications of this biological, clinical, and epidemiological diversity are incompletely understood. The importance of investigating etiology by NHL subtype is clearly supported by research on immunosuppression, infections, and autoimmune diseases, which are the strongest and most e…

Rationale and Design of the International Lymphoma Epidemiology Consortium (InterLymph) Non-Hodgkin Lymphoma Subtypes Project

Background: Non-Hodgkin lymphoma (NHL), the most common hematologic malignancy, consists of numerous subtypes. The etiology of NHL is incompletely understood, and increasing evidence suggests that risk factors may vary by NHL subtype. However, small numbers of cases have made investigation of subtype-specific risks challenging. The International Lymphoma Epidemiology Consortium therefore undertook the NHL Subtypes Project, an international collaborative effort to investigate the etiologies of NHL subtypes. This article describes in detail the project rationale and design. Methods: We pooled individual-level data from 20 case-control studies (17 471 NHL cases, 23 096 controls) from North Ame…

Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10…

Expression of the multidrug resistance glycoprotein 170 in the peripheral blood lymphocytes of rheumatoid arthritis patients. The percentage of lymphocytes expressing glycoprotein 170 is increased in patients treated with prednisolone

International audience; Abstract: The objective was to evaluate the expression of the multidrug resistance P-glycoprotein (P-gp) in peripheral blood lymphocytes (PBL) of patients with rheumatoid arthritis (RA). PBL from 68 RA patients and 44 controls were evaluated. RA patients had a mean disease duration of 10.7 yr, with a mean number of past resistances to DMARDs of 0.82, and were treated with NSAIDs (n = 34), DMARDs (n = 25) and prednisolone (n = 40). Fluorescence flow cytometry was used to assess P-gp membrane expression on PBL. In the RA group, the percentage of PBL expressing P-gp was higher in patients treated with prednisolone than in other patients [mean +/- S.D.: 10.7 +/- 15.8% vs…

Correction: Association of ionizing radiation dose from common medical diagnostic procedures and lymphoma risk in the Epilymph case-control study

International audience; 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 mar…

Factors related to the relative survival of patients with diffuse large B-cell lymphoma in a population-based study in France: does socio-economic status have a role?

IF 7.702; International audience; 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 p…

Testicular germ-cell tumours and penile squamous cell carcinoma: Appropriate management makes the difference

Germ-cell tumours (GCT) of the testis and penile squamous cell carcinoma (PeSCC) are a rare and a very rare uro-genital cancers, respectively. Both tumours are well defined entities in terms of management, where specific recommendations - in the form of continuously up-to-dated guide lines- are provided. Impact of these tumour is relevant. Testicular GCT affects young, healthy men at the beginning of their adult life. PeSCC affects older men, but a proportion of these patients are young and the personal consequences of the disease may be devastating. Deviation from recommended management may be a reason of a significant prognostic worsening, as proper treatment favourably impacts on these t…

Epidemiology of rare cancers and inequalities in oncologic outcomes

Rare cancers epidemiology is better known compared to the other rare diseases. Thanks to the long history of the European population-based cancer registries and to the EUROCARE huge database, the burden of rare cancers has been estimated the European (EU28) population. A considerable fraction of all cancers is represented by rare cancers (24%). They are a heterogeneous group of diseases, but they share similar problems: uncertainty of diagnosis, lack of therapies, poor research opportunities, difficulties in clinical trials, lack of expertise and of centres of reference. This paper analyses the major epidemiological indicators of frequency (incidence and prevalence) and outcome (5-year surv…

Exposure to UV radiation and risk of Hodgkin lymphoma: A pooled analysis

Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320HLcasesand 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inv…

Treatment challenges in and outside a network setting: Head and neck cancers.

Head and neck cancer (HNC) is a rare disease that can affect different sites and is characterized by variable incidence and 5-year survival rates across Europe. Multiple factors need to be considered when choosing the most appropriate treatment for HNC patients, such as age, comorbidities, social issues, and especially whether to prefer surgery or radiation-based protocols. Given the complexity of this scenario, the creation of a highly specialized multidisciplinary team is recommended to guarantee the best oncological outcome and prevent or adequately treat any adverse effect. Data from literature suggest that the multidisciplinary team-based approach is beneficial for HNC patients and lea…

Outcome of Refractory Anemia with Ringed Sideroblasts Associated with Marked Thrombocytosis (RARS-T) In a Large Cohort of Patients

Abstract Abstract 4113 Introduction: Most of the data related to RARS-T, a rare disorder, involve small cohorts of patients. We aimed to analyze more patients also considering a variety of myelodysplastic or myeloproliferative disorders. Objective: To compare a large cohort of patients with RARS-T to refractory anemia with ringed sideroblasts (RARS), refractory anemia with ringed sideroblasts and multilineage dysplasia (RARS-MD) or essential thrombocythemia (ET) at the time of diagnosis and during disease evolution, in terms of survival and complications. Materials: Data of a European multi-center study was used including 199 cases of RARS-T 173 cases of RARS, 102 cases of RARS-MD and 431 c…

Occupational exposure to endocrine disruptors and lymphoma risk in a multi-centric European study

Background: Incidence rates of lymphoma are usually higher in men than in women, and oestrogens may protect against lymphoma. Methods: We evaluated occupational exposure to endocrine disrupting chemicals (EDCs) among 2457 controls and 2178 incident lymphoma cases and subtypes from the European Epilymph study. Results: Over 30 years of exposure to EDCs compared to no exposure was associated with a 24% increased risk of mature B-cell neoplasms (P-trend=0.02). Associations were observed among men, but not women. Conclusions: Prolonged occupational exposure to endocrine disruptors seems to be moderately associated with some lymphoma subtypes. © 2015 Cancer Research UK. All rights reserved.

Estimation de l’incidence des hémopathies malignes en France entre 1980 et 2012

International audience; BACKGROUND:The classification of hematological malignancies (HMs) has changed in recent decades. For the first time, the French network of cancer registries (Francim) provides estimates for incidence and trends of HM in France between 1980 and 2012 for major HM subtypes.METHODS:Incidence was directly estimated by modeling the incidence rates measured in the cancer registry area. For each HM subtype, a "usable incidence period" was defined a priori, corresponding to the years for which all the registries collected them in a homogeneous way. For both sexes and each HM subtype, age-period-cohort models were used to estimate national incidence trends.RESULTS:Overall in F…

Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC)

AbstractBackground: 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/m…

The heterogeneity of changes in incidence and survival among lymphoid malignancies in a 30-year French population-based registry.

Our specialized population-based registry has allowed us to explore changes in incidence and survival by subtype over the last 30 years. Between 1980 and 2009, 4790 cases of lymphoid malignancies were registered using the International Classification of Diseases for Oncology. The incidence rate of lymphoid malignancies was 20.5 per 100,000 inhabitants per year, and ranged from 0.1 to 4 according to subtype. Five-year net survival was 65%, and ranged from 41% to 93% according to subtype. We observed an increase in 5-year net survival between the periods 1980-1989 and 2000-2009 (58% vs. 70%). This was observed in most but not all subtypes. Our long-standing population-based registry allowed u…

Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours

Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network.

Splenic Marginal Zone Lymphoma: French Registries Population-Based Treatment and Survival Analyses (2002-2014)

Background. Splenic Marginal Zone Lymphoma (SMZL) is a rare indolent B-cell lymphoma characterized by a massive splenomegaly and a moderate lymphocytosis. There is no standard of care for SMZL so far. The treatment is indicated if constitutional symptoms, massive splenomegaly and/or cytopenia, after a watch and wait period that is highly variable. Rituximab with or without chemotherapy, chemotherapy, and splenectomy are valid treatment approaches. Our objectives were to describe the characteristics of the patients with SMZL retrospectively collected from a French population database, to analyze the treatments received in first line (Tt1) and in second line (Tt2) in term of efficacy, and to …

Epidemiology of Mantle Cell Lymphoma: A Population-Based Study in France

Abstract Abstract 5222 Introduction: Mantle cell lymphoma (MCL) is an aggressive and rare B-cell lymphoma entity representing around 5–8% of non-Hodgkin's lymphomas in adults. To our knowledge no data is available on the epidemiology of MCL in France. We aimed to describe incidence, survival and main clinical characteristics of MCL in a French population. Methods: Patients diagnosed with MCL were identified in three administrative areas covered by an haematological malignancies registry: the Côte d'Or (from 1988 to 2008), the Basse-Normandie (from 1997 to 2006) and the Gironde (from 2002 to 2006). Main clinical features and management characteristics were collected. World age-standardised …

A pooled analysis of alcohol consumption and risk of multiple myeloma in the international multiple myeloma consortium

Abstract Background: Recent findings suggest that alcohol consumption may reduce risk of multiple myeloma. Methods: To better understand this relationship, we conducted an analysis of six case–control studies participating in the International Multiple Myeloma Consortium (1,567 cases, 7,296 controls). Summary ORs and 95% confidence intervals (CI) relating different measures of alcohol consumption and multiple myeloma risk were computed by unconditional logistic regression with adjustment for age, race, and study center. Results: Cases were significantly less likely than controls to report ever drinking alcohol (men: OR = 0.72; 95% CI, 0.59–0.89; women: OR = 0.81; 95% CI, 0.68–0.95). The inv…

Unbiased estimates of long-term net survival of hematological malignancy patients detailed by major subtypes in France.

Long-term population-based survival data detailed by cancer subtype are important to measure the overall outcomes of malignancy managements. We provide net survival estimates at 1, 3, 5 and 10-year postdiagnosis on 37,549 hematological malignancy (HM) patients whose ages were >15 years, diagnosed between 1989 and 2004 and actively followed until 2008 by French population-based cancer registries. These are, to our knowledge, the first unbiased estimates of 10-year net survival in HMs detailed by subtypes. HMs were classified according to the International Classification of Diseases-Oncology 3. Net survival was estimated with the unbiased Pohar-Perme method. The results are reported by sex an…

Tendances de prescription de l’hormonothérapie et survie chez les femmes atteintes d’un cancer du sein non métastatique à récepteurs hormonaux positifs traitées par hormonothérapie - Étude sur base de données populationnelle

Introduction La plupart des donnees sur l’efficacite de l’hormonotherapie proviennent d’essais cliniques randomises. Peu ou moins de donnees existent sur l’efficacite de l’hormonotherapie en vie reelle et sa prescription au cours du temps. Cette etude avait pour objectif d’identifier les facteurs pronostiques de la survie chez les femmes atteintes d’un cancer du sein non metastatique a recepteurs hormonaux positifs (RH +). Methodes Une etude observationnelle retrospective a ete realisee a partir du Registre des cancers du sein et autres cancers gynecologiques de Cote d’Or en France. Toutes les femmes ayant recu un diagnostic de cancer du sein RH + invasif primaire non metastatique entre 199…

Épidémiologie des leucémies aiguës

Resume Les leucemies aigues, lymphoides et myeloides representent 10 a 15% des hemopathies malignes et sont des affections rares qui en dehors de quelques formes sont souvent de pronostic pejoratif. Les leucemies aigues myeloides (LAM) ont une incidence stable au cours du temps qui varie de 2,5 a 3,5/100 000 habitants/an dans les pays occidentaux. L’âge median de survenue est de 63 ans. En dehors des formes avec anomalies cytogenetiques recurrentes, en particulier les LA promyelocytaires qui ont une survie a 5 ans voisine de 60%, les LAM ont une survie a 5 ans inferieure a 20% et qui ne s’ameliore pas au fil du temps. Les leucemies aigues lymphoblastiques (LAL) ont une incidence proche de 1…

Survival variations by country and age for lymphoid and myeloid malignancies in Europe 2000–2007: Results of EUROCARE-5 population-based study

BACKGROUND: Significant advances in the management of patients with lymphoid and myeloid malignancies entered clinical practice in the early 2000's. The EUROCARE-5 study database provides an opportunity to assess the impact of these changes at the population level by country in Europe. We provide survival estimates for clinically relevant haematological malignancies (HM), using the International Classification of Diseases for Oncology 3, by country, gender and age in Europe. METHODS: We estimated age-standardised relative survival using the complete cohort approach for 625, 000 adult patients diagnosed in 2000-2007 and followed up to 2008. Survival information was provided by 89 participati…

Lymphoma occurring in patients over 90 years of age: characteristics, outcomes, and prognostic factors. A retrospective analysis of 234 cases from the LYSA.

International audience; BACKGROUND: Lymphoma occurring in patients aged 90 or older is not uncommon, and its incidence is expected to increase over time. Management of these patients is difficult given their underlying fragility and the lack of information regarding this population. PATIENTS AND METHODS: We retrospectively analyzed 234 patients diagnosed with lymphoma at the age of 90 years or older (90+) between 1990 and 2012 to describe their characteristics, management, outcomes and prognostic factors. RESULTS: The median age was 92 years; 88% were B-cell lymphomas consisting mainly in diffuse large B-cell lymphoma. The median overall survival (OS) was 7.2 months (range, 0-92 months) for…

Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes

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 o…

InterLymph hierarchical classification of lymphoid neoplasms for epidemiologic research based on the WHO classification (2008): update and future directions

Abstract After publication of the updated World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues in 2008, the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph) now presents an update of the hierarchical classification of lymphoid neoplasms for epidemiologic research based on the 2001 WHO classification, which we published in 2007. The updated hierarchical classification incorporates all of the major and provisional entities in the 2008 WHO classification, including newly defined entities based on age, site, certain infections, and molecular characteristics, as well as borderline categories, early and “in situ” …

Incidence and Prognostic Value of FLT-3 and NPM1 Genes Abnormalities in Acute Myeloid Leukemia in the Côte D’or Population, France

Abstract Context: In acute myeloid leukemia (AML), the recently described FLT-3 and NPM1 genes abnormalities were found to have a prognostic value in AML with normal karyotype and a specific therapeutic strategy was proposed according to these abnormalities. We look for the incidence and prognostic value of these abnormalities in cases diagnosed on a well defined population. Material and Methods: AML diagnosed according to WHO classification between 01/01/2001 and 31/12/2006 in the population of the Côte d’Or department, were included. Karyotype analyses were performed in 81% of the cases. The FLT3 D835 mutation, the FLT3 internal duplication (ITD) and the NPM1 mutation were systematically…

Trends in excess mortality in follicular lymphoma at a population level

Background Since the 1990s and since the development of humanised monoclonal antibodies in 1998, the treatment of non-Hodgkin lymphoma has undergone profound changes. Follicular lymphoma (FL) was the first to benefit from this treatment, and several clinical trials have shown a significant improvement in overall survival, but little information is available at a population level. Objective Our objective was to estimate changes in FL-specific mortality at a population level, with an appropriate methodology. Methods Two French retrospective population-based studies on FL were conducted, one from 1995 to 2004, in 1477 patients, and one from 1995 to 2010, in 451 patients. Trends in excess morta…

HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes

Abstract 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…

Medical history, lifestyle, family history, and occupational risk factors for chronic lymphocytic leukemia/small lymphocytic lymphoma: The InterLymph non-Hodgkin lymphoma subtypes project

Background: Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are two subtypes of non-Hodgkin lymphoma. A number of studies have evaluated associations between risk factors and CLL/SLL risk. However, these associations remain inconsistent or lacked confirmation. This may be due, in part, to the inadequate sample size of CLL/SLL cases. Methods: We performed a pooled analysis of 2440 CLL/SLL cases and 15 186 controls from 13 case-control studies from Europe, North America, and Australia. We evaluated associations of medical history, family history, lifestyle, and occupational risk factors with CLL/SLL risk. Multivariate logistic regression analyses were used to estimate …

Pancreatic cancer: Wait times from presentation to treatment and survival in a population-based study

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 bet…

Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF in a case of atypical B-cell chronic lymphocytic leukemia harboring a t(14;18)(q32;q21)

Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) is usually straightforward, involving clinical, immunophenotypic (Matutes score), and (immuno)genetic analyses (to refine patient prognosis for treatment). CLL cases with atypical presentation (e.g., Matutes ≤ 3) are also encountered, and for these diseases, biology and prognostic impact are less clear. Here we report the genomic characterization of a case of atypical B-CLL in a 70-yr-old male patient; B-CLL cells showed a Matutes score of 3, chromosomal translocation t(14;18)(q32;q21) (BCL2/IGH), mutated IGHV, deletion 17p, and mutations in BCL2, NOTCH1 (subclonal), and TP53 (subclonal). Quite strikingly, a novel PAX5 mutation that w…

Les néoplasies plasmocytaires et autres dysglobulinémies en population générale

Resume Les neoplasies plasmocytaires occupent en 2012 en France le premier rang des hemopathies malignes en nombre. Majo-ritairement il s’agit de myelome multiple ou de plasmocytome (MM/P) mais on retrouve aussi des pathologies de severite variable. La classification OMS actuelle definit les gammapathies monoclonales de signification indeterminee en une entite a part entiere. Des progres importants dans la prise en charge de ces pathologies ont ete realises grâce a une meilleure connaissance de la maladie et a l’utilisation de nouvelles molecules therapeutiques. Ces progres peuvent etre visualises par l’etude des tendances d’indicateurs epidemiologiques en population generale. Les donnees f…

Associations of non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci.

Autoimmune conditions and immune system-related genetic variations are associated with risk of non-Hodgkin lymphoma (NHL). In a pooled analysis of 8,692 NHL cases and 9,260 controls from 14 studies (1988-2007) within the International Lymphoma Epidemiology Consortium, we evaluated the interaction between immune system genetic variants and autoimmune conditions in NHL risk. We evaluated the immunity-related single nucleotide polymorphisms rs1800629 (tumor necrosis factor gene (TNF) G308A), rs1800890 (interleukin-10 gene (IL10) T3575A), rs6457327 (human leukocyte antigen gene (HLA) class I), rs10484561 (HLA class II), and rs2647012 (HLA class II)) and categorized autoimmune conditions as prim…

Increased Risk of Acute Myeloid Leukemias and Myelodysplastic Syndromes in Patients Who Received Thiopurine Treatment for Inflammatory Bowel Disease.

Background & Aims Treatment with immunosuppressive thiopurines such as azathioprine is associated with an increased risk of leukemogenesis. We assessed the risk of myeloid disorders, such as acute myeloid leukemia and myelodysplastic syndromes, in a large cohort of patients with inflammatory bowel disease (IBD) in France. Methods We performed a prospective observational study of 19,486 patients with IBD enrolled in the Cancers Et Surrisque Associe aux Maladies inflammatoires intestinales En France (CESAME) study from May 2004 through June 2005; patients were followed through December 31, 2007. The incidence of myeloid disorders in the general population, which was used for reference, was de…

Caractérisation de l’anémie hémolytique auto-immune associée aux hémopathies lymphoïdes à partir du registre des hémopathies malignes de Côte d’Or

Introduction L’anemie hemolytique auto-immune (AHAI) est une cytopenie auto-immune (CAI) caracterisee par une destruction des globules rouges par des auto-anticorps diriges contre certains de leurs antigenes de surface. Son incidence est estimee entre 1 et 3/100 000 personnes-annees (PA). Les AHAI a auto-anticorps chauds sont les plus frequentes et les formes secondaires, observees dans la moitie des cas, ont tendance a augmenter avec l’âge, notamment en association aux hemopathies malignes. Les donnees de la litterature reposent cependant sur de faibles cohortes ou des centres tertiaires, avec un possible biais de recrutement. L’objectif de notre etude est de decrire la frequence de l’AHAI…

Clinical Features And Course Of Refractory Anemia With Ring Sideroblasts Associated With Marked Thrombocytosis

Background Refractory anemia with ring sideroblasts associated with marked thrombocytosis was proposed as a provisional entity in the 2001 World Health Organization classification of myeloid neoplasms and also in the 2008 version, but its existence as a single entity is contested. We wish to define the clinical features of this rare myelodysplastic/myeloproliferative neoplasm and to compare its clinical outcome with that of refractory anemia with ring sideroblasts and essential thrombocythemia. Design and Methods We conducted a collaborative retrospective study across Europe. Our database included 200 patients diagnosed with refractory anemia with ring sideroblasts and marked thrombocytosis…

Impact de l’âge et de l’année sur les indicateurs de survie nette et de guérison par sous-type de leucémie aiguë myéloïde en France entre 1989 et 2010

Etat de la question Estimer la survie nette et les indicateurs guerison par sous-type de leucemie aigue myeloide (LAM) en France. Materiel et methodes Au total, 6460 cas de LAM dont l’âge ≥ 15 ans, diagnostiques entre 1989 et 2010 ont ete inclus. Cinq sous-types de LAM ont ete definis a l’aide de la classification ICD-O-3 et HAEMACARE. La survie nette a ete obtenue en utilisant le modele flexible ajuste sur l’âge, le sexe et l’annee de diagnostic pour chaque sous-type de LAM. Lorsque l’hypothese de guerison etait acceptable, un modele de guerison flexible a ete utilise pour estimer la proportion de gueri (P), le temps de guerison (TTC) et le temps de survie median pour les patients non guer…

Occupational exposure to immunologically active agents and risk for lymphoma: The European Epilymph case-control study

Objectives: Allergies and asthma may be protective for the development of lymphoma. We evaluated whether occupational allergens that provoke immune reactivity and asthma through an IgE-mediated pathway are protective for lymphoma. Methods: The Epilymph study includes histologically or cytologically confirmed Hodgkin, B-cell, and T-cell lymphoma cases from six European countries (Spain, France, Germany, Italy, Ireland, and Czech Republic) recruited in 1998-2004. Controls were frequency matched to cases by age, gender, and study centre. Lifetime occupational exposure to seven high molecular weight (HMW) agents was evaluated through an asthma-specific job-exposure matrix. 2205 lymphoma cases a…

Prédiction de la réponse aux traitements de fond antirhumatismaux (DMARD) dans la polyarthrite rhumatoïde

Resume Objectif Examiner les facteurs potentiels predictifs de la reponse aux traitements de fond (DMARD) classiques dans la polyarthrite rhumatoide (PR). Methodes (1) design de l’etude : etude prospective sur six mois de suivi. Participants  : patients avec une PR active ; (2) intervention et suivi : introduction d’un DMARD. Reponse au traitement evaluee a six mois (criteres ACR20) ; (3) analyse : facteurs potentiels predictifs de la reponse : criteres demographiques, activite de la maladie, pourcentages de sous-populations de cellules mononucleees du sang peripherique (CMSP) exprimant la glycoproteine P, taux d’interleukine 1 beta (IL-1β) serique, IL-6, IL-8, IL-10, IL-12 et de facteur de…

Occupation and Risk of Non-Hodgkin Lymphoma and Its Subtypes: A Pooled Analysis from the InterLymph Consortium

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 det…

Tumor necrosis factor (TNF) and lymphotoxin-a (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium

In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G>A (rs1800629), lymphotoxin-alpha (LTA) 252A>G (rs909253), IL10 -3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-…

Non-Hodgkin lymphoma and obesity: A pooled analysis from the InterLymph consortium

Nutritional status is known to alter immune function, a suspected risk factor for non-Hodgkin lymphoma (NHL). To investigate whether long-term over, or under, nutrition is associated with NHL, self-reported anthropometric data on weight and height from over 10,000 cases of NHL and 16,000 controls were pooled across 18 case-control studies identified through the International Lymphoma Epidemiology Consortium. Study-specific odds ratios (OR) were estimated using logistic regression and combined using a random-effects model. Severe obesity, defined as BMI of 40 kg m-2 or more, was not associated with NHL overall (pooled OR = 1.00, 95% confidence interval (CI) 0.70-1.41) or the majority of NHL …

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

International audience; 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 g…

Immunologic effects of rituximab on the human spleen in immune thrombocytopenia

Abstract Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell–related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell de…

Caractérisation de la thrombopénie immunologique associée aux hémopathies lymphoïdes à partir du registre des hémopathies malignes de Côte d’Or

Introduction Le purpura thrombopenique immunologique (PTI) est une cytopenie auto-immune (CAI) caracterisee par une diminution de la duree de vie des plaquettes liee a la fois a leur destruction peripherique par les macrophages spleniques et a un defaut de production medullaire. Son incidence est estimee entre 3 et 4/100 000 personnes-annees (PA). S’il est le plus souvent primaire, il est associe dans 15–20 % des cas a d’autres maladies auto-immunes ou a des hemopathies malignes. Pour ces dernieres, les associations les plus frequentes sont rapportees avec la leucemie lymphoide chronique (LLC), la leucemie a grands lymphocytes T granuleux (LGL) et le lymphome de Hodgkin (LH) mais les donnee…

A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus

Contains fulltext : 137763.pdf (Publisher’s version ) (Open Access) Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI)=0.76-0.86, Pcombined=3.5 x 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regul…

Geographical Disparities in Multiple Myeloma Survival in Three French Regions

Abstract Introduction: Within the past decade, new therapeutic agents for Multiple Myeloma (MM) have improved survival of patients included in clinical trials. The aim of this study was to measure and compare characteristics and survival of patients with MM in different French regions in the general population. Methods: All incident cases with MM (ICD-O-3 codes, 9732/3 and) between January 1, 2008 and December 31, 2009 in the French population-based Hematological Malignancies registries (Calvados, Côte d'Or and Gironde) were included. The end point of follow-up was January 1, 2015. Specific clinical information was recorded from clinical charts. Incidence rates were calculated using estimat…

Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis

IF 15.132 (2017); International audience; 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…

A Pooled Analysis of Reproductive Factors, Exogenous Hormone Use, and Risk of Multiple Myeloma among Women in the International Multiple Myeloma Consortium

Abstract 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 estima…

Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph)

Kamper-Jorgensen, M Rostgaard, K Glaser, S L Zahm, S H Cozen, W Smedby, K E Sanjose, S Chang, E T Zheng, T La Vecchia, C Serraino, D Monnereau, A Kane, E V Miligi, L Vineis, P Spinelli, J J McLaughlin, J R Pahwa, P Dosman, J A Vornanen, M Foretova, L Maynadie, M Staines, A Becker, N Nieters, A Brennan, P Boffetta, P Cocco, P Hjalgrim, H eng 5 ROI CA69269/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2013/06/22 06:00 Ann Oncol. 2013 Sep;24(9):2245-55. doi: 10.1093/annonc/mdt218. Epub 2013 Jun 19.; International audience; BACKGROUND: The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smok…

Mesothelioma and thymic tumors: Treatment challenges in (outside) a network setting.

The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMI…

Leucocytosis and thrombosis at diagnosis are associated with poor survival in polycythaemia vera: a population-based study of 327 patients

Three hundred and twenty-seven patients from two population-based cohorts with an established diagnosis of polycythaemia vera were studied for prognostic risk factors for survival and leukaemia in a long-term survey. The relative survival (RS) was 72% and 46% at 10 and 20 years respectively, from the time of diagnosis. Multivariate analysis identified age >70 years, white blood cell count >13 × 10(9) /l and thrombo-embolism at diagnosis as independent risk factors. Patients with two or three of these factors had a 10 year RS of 26%, compared with 59% and 84% in patients with one and no risk factors, respectively. Age and leucocyte count are the main predicting factors for survival in polycy…

Calreticulin Mutations in Myeloproliferative Neoplasms: Comparison of Three Diagnostic Methods

International audience; Calreticulin (CALR) mutations have recently been reported in 70-84% of JAK2V617F-negative myeloproliferative neoplasms (MPN), and this detection has become necessary to improve the diagnosis of MPN. In a large single-centre cohort of 298 patients suffering from Essential Thrombocythemia (ET), the JAK2V617F, CALR and MPL mutations were noted in 179 (60%), 56 (18.5%) and 13 (4.5%) respectively. For the detection of the CALR mutations, three methods were compared in parallel: high-resolution melting-curve analysis (HRM), product-sizing analysis and Sanger sequencing. The sensitivity for the HRM, product-sizing analysis and Sanger sequencing was 96.4%, 98.2% and 89.3% re…

Extracorporeal circuit heparinization in selective low density lipoprotein apheresis: changes in patient hemostasis and low molecular weight heparin benefit.

Treatment by low density lipoprotein (LDL) apheresis using dextran sulfate columns (DSC) leads to hemostasis alterations with prolonged activated partial thromboplastin time (APTT) of more than 120 seconds. In order to explain this hypocoagulability, we studied hemostasis parameters both in patients and in the extracorporeal circulation (ECC). Hemostasis changes are first related to unfractionated heparin (UFH)—needed to avoid circuit coagulation—which leads to high residual heparinemia in the patient (more than 3 times the recommended level for therapeutic use). Second, the hypocoagulability is induced by a coagulation factor decrease (primarily factors V, VIH, and X) mainly due to an adso…

Incidence of chronic myeloid leukemia and patient survival: results of five French population-based cancer registries 1980-2009.

The treatment of chronic myeloid leukemia (CML) has seen several major advances over the past 30 years, notably with the introduction of interferon followed by Bcr-Abl tyrosine kinase inhibitors. We analyzed trends in the incidence of CML and patient survival in France. All cases recorded in five population-based registries between 1980 and 2009 were included. European (ESR) and world (WSR) standardized incidence rates as well as relative survival (RS) rates were estimated. We analyzed data for 781 patients (9863/3: 13.6%; 9875/3: 82.2%; 9876/3: 4.2%). ESR was 1.02 [95% confidence interval (CI) = 0.93-1.11] and WSR was 0.81 [95% CI = 0.72-0.90]. The five RS rates among patients with Philade…

Leukocytosis is associated with poor survival but not with increased risk of thrombosis in essential thrombocythemia: a population-based study of 311 patients

Leukocytosis is associated with poor survival but not with increased risk of thrombosis in essential thrombocythemia: a population-based study of 311 patients

AML transformation in 56 patients with Ph- MPD in two well defined populations.

The Philadelphia chromosome-negative (Ph-) chronic myeloproliferative disorders (MPD) have an inherent tendency for transformation into acute myelogenous leukaemia (AML). The long-term rate of leukaemic transformation in unselected MPD patients was studied in well-defined MPD populations in Gothenburg, Sweden and the Cote d'Or area, Burgundy, France, respectively. Over a median observation time of 15 yr, 56 subjects (7%) out of a total of 795 patients with Ph- MPD transformed to AML. The yearly incidence of AML transformation was 0.38% in polycythaemia vera (PV), 0.37% in essential thrombocythaemia (ET) and 1.09% in idiopathic myelofibrosis (IMF). The incidence of AML development was signif…

Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet—a population-based study

Background: Rare cancers pose challenges for diagnosis, treatments, and clinical decision making. Information about rare cancers is scant. The RARECARE project defined rare cancers as those with an annual incidence of less than six per 100 000 people in European Union (EU). We updated the estimates of the burden of rare cancers in Europe, their time trends in incidence and survival, and provide information about centralisation of treatments in seven European countries. Methods: We analysed data from 94 cancer registries for more than 2 million rare cancer diagnoses, to estimate European incidence and survival in 2000–07 and the corresponding time trends during 1995–2007. Incidence was calcu…

A pooled analysis of cigarette smoking and risk of multiple myeloma from the international multiple myeloma consortium.

Abstract Background: Past investigations of cigarette smoking and multiple myeloma have been underpowered to detect moderate associations, particularly within subgroups. To clarify this association, we conducted a pooled analysis of nine case–control studies in the International Multiple Myeloma Consortium, with individual-level questionnaire data on cigarette smoking history and other covariates. Methods: Using a pooled population of 2,670 cases and 11,913 controls, we computed odds ratios (OR) and 95% confidence intervals (CI) relating smoking to multiple myeloma risk using unconditional logistic regression adjusting for gender, age group, race, education, body mass index, alcohol consump…

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3): analysis of individual data from 258 cancer registries in 61 countries

BACKGROUND Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes a…

TRANSLOCATIONS INVOLVING 5q3 5 MAY ALSO BE ASSOCIATED WITH PLASMA CELL LEUKAEMIA

Risk assessment of second primary cancer according to histological subtype of non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of diseases that are known to carry a considerable risk of second primary cancer (SPC). However, little attention has been paid to SPC risk assessment according to NHL subtypes. Data from 10 French population-based cancer registries were used to establish a cohort of 7546 patients with a first diagnosis of NHL (eight subtypes) between 1989 and 2004. Standardized incidence ratios (SIRs) of metachronous SPC were estimated. Among the 7546 patients diagnosed with a NHL, the overall SPC risk was 25% higher than that in the reference population (SIR = 1.25, 95% confidence interval 1.15–1.36). In univariate analysis, the SPC risk differed…

Trends in Incidence and Survival of Myeloid Malignancies Since 1980, in the Côte D'or Department, Burgundy, France.

Abstract Abstract 3122 Poster Board III-59 Objective The Registry of Haematological Malignancies (HM) has been established on January 1st, 1980 in the department of Côte d'Or (pop 500 000 inhabitants). It was the first specialized registry in haematology in the world. During the course of 25 years (1980-2004), 5026 cases of HM were recorded including 1553 Myeloid malignancies (MM) in which entities not initially considered as malignant were taken in account such as Myelodysplastic syndrome (MDS) and some Myeloproliferative neoplasms (MPN). This allow us to present trends in incidence and survival of myeloid malignancies by entities since 1980. Method MM diagnosed in the population between …

Atopic disease and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis

AbstractWe performed a pooled analysis of data on atopic disease and risk of non–Hodgkin lymphoma (NHL) from 13 case-control studies, including 13,535 NHL cases and 16,388 controls. Self-reported atopic diseases diagnosed 2 years or more before NHL diagnosis (cases) or interview (controls) were analyzed. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were computed in two-stage random-effects or joint fixed-effects models, and adjusted for age, sex, and study center. When modeled individually, lifetime history of asthma, hay fever, specific allergy (excluding hay fever, asthma, and eczema), and food allergy were associated with a significant reduction in NHL risk, and there wa…

Leukocytosis and Thrombosis At Diagnosis Are Associated with Poor Survival in Polycythemia Vera: A Population-Based Study on 327 Patients

Abstract Abstract 2819 Introduction Polycythemia Vera (PV) is a myeloproliferative neoplasm with a long life expectancy. Consequently, long-term follow-up studies that focus on survival of PV patients must be conducted in order to register a sufficient number of events to provide informative results and statistical analyses. Most of the published studies are single-institution that focused on patients referred to hospitals, which does not necessarily reflect the course of PV in the general population. In these studies, the median age at diagnosis is younger than usually noted for PV patients in population-based studies. Moreover, survival is generally based on observed mortality, a good but…

Survival of Myeloid Malignancies in EUROPE: Results of the HAEMACARE Project.

Abstract Abstract 3911 Poster Board III-847 Background Updated ICD-O and WHO classifications of Haematological Malignancies (HMs) take into account cell lineage, genotype, morphological aspects, immuno-histochemical and genetic characteristics, and clinical behaviour of the disease, dividing Lymphoid and Myeloid neoplasms in subcategories with possible similar aetiology or prognosis. Thus, good quality of morphological data on HMs is capital. The HAEMACARE project aimed to increase standardization and the availability of Cancer Registries (CRs) morphological data on HMs, in order to improve comparability of incidence, survival and prevalence across Europe. This study aims to present the HAE…

Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32

To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 × 10-29 and rs7755224, combined P = 2.00 × 10-19; r2 = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 × 10-9). © 2010 Nature America, Inc. All rights reserved.

Association of JAK-STAT pathway related genes with lymphoma risk: results of a European case-control study (EpiLymph)

Previous studies have suggested an important role for the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling pathway in tumour development. Therefore, we explored genetic variants in JAK-STAT pathway associated genes with lymphoma risk. In samples of the EpiLymph case-control study we genotyped 1536 single nucleotide polymorphisms (SNPs) using GoldenGate BeadArray™ Technology (Illumina, San Diego, CA, USA). Here, we report the associations between selected SNPs and haplotypes of the JAK-STAT pathway and risk of Hodgkin lymphoma (HL), B-cell non-Hodgkin lymphoma (B-NHL) and most frequent B-NHL subtypes. Among 210 relevant JAK-STAT pathway-related SNPs, polymo…

Towards optimal clinical and epidemiological registration of haematological malignancies: Guidelines for recording progressions, transformations and multiple diagnoses

AbstractHaematological malignancies (HM) represent over 6% of the total cancer incidence in Europe and affect all ages, ranging between 45% of all cancers in children and 7% in the elderly. Thirty per cent of childhood cancer deaths are due to HM, 8% in the elderly. Their registration presents specific challenges, mainly because HM may transform or progress in the course of the disease into other types of HM. In the context of cancer registration decisions have to be made about classifying subsequent notifications on the same patient as the same tumour (progression), a transformation or a new tumour registration. Allocation of incidence date and method of diagnosis must also be standardised…

Prediction of response to disease modifying antirheumatic drugs in rheumatoid arthritis.

Abstract Aim To investigate potential predictors of response to conventional DMARDs in RA. Methods Study design – 6-month follow-up prospective study. Participants RA patients with active disease. Intervention and follow-up Introduction of one DMARD. Response to treatment evaluated at 6 months (ACR20 criteria). Analysis Potential predictors of response, patients’ demographics, disease activity, percentages of PBMC subsets expressing P-gp, serum IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α levels, were evaluated using univariate and multivariate logistic regression analysis. ROC curve analyses were performed in order to obtain thresholds allowing the prediction of response. Results Forty-two patie…

Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P<5 × 10−…

Antibodies against lytic and latent Kaposi's sarcoma-associated herpes virus antigens and lymphoma in the European EpiLymph case-control study.

Background: Kaposi's sarcoma-associated herpes virus is associated with primary effusion lymphoma and multicentric Castleman's disease. Methods: Seropositivity to lytic and latent Kaposi's sarcoma herpes virus (KSHV) antigens were examined in 2083 lymphomas and 2013 controls from six European countries. Results: Antibodies against KSHV latent and lytic antigens were detectable in 4.5% and 3.4% of controls, respectively, and 3.6% of cases (P>0.05). The KSHV seropositivity was associated with splenic marginal zone lymphoma (SMZL) (odds ratio (OR)=4.11, 95% confidence interval (CI)=1.57–10.83) and multiple myeloma (OR=0.31, 95% CI=0.11–0.85). Conclusion: The KSHV is unlikely to contribute impo…

Second Cancer Incidence Among Chronic Lymphocytic Leukemia (CLL) Patients: A French Population-Based Study

Abstract Introduction. The risk of developing a second primary cancer (SPC) is increased in patients with CLL. The mechanisms explaining this association could be related to lifestyle, environment, host factors or interactions or other influences. We conducted an epidemiological study based on 10 French registries and evaluated the risk of developing SPC in patients with CLL. Methods. Data from French population-based registries were used to establish a cohort of all patients diagnosed with a first cancer between 1989 and 2004 and followed-up until December 31, 2007. The person-year approach was used to estimate Standardized Incidence Ratios (SIRs) and Excess Absolute Risks (EARs) of metach…

A Novel Risk Locus at 6p21.3 for Epstein-Barr Virus-Positive Hodgkin Lymphoma

Abstract Background: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein–Barr virus (EBV) status, particularly within the MHC region. Methods: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (cHL) cases and 5,726 control subjects of European origin. Notable findings were genotyped in an independent study population of 468 cHL cases and 551 controls. Results: We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interva…