Risk Factors and Causes of Death in MEN1 Disease. A GTE (Groupe d’Etude des Tumeurs Endocrines) Cohort Study Among 758 Patients

Goudet, P.; Murat, A.; Binquet, Christine; Cardot-Bauters, C.; Costa, Ana; Ruszniewski, Philippe; Niccoli, Patricia; Ménégaux, Fabrice; Chabrier, G.; Borson‐Chazot, Françoise; Tabarin, Antoine; Bouchard, Philippe; Delemer, Brigitte; Beckers, Albert; Bonithon‐Kopp, Claire

doi:10.1007/s00268-009-0290-1

Cited by 303 publications

(362 citation statements)

References 45 publications

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“…This last category includes 73 patients. They were considered with caution and selected after a critical case-by-case analysis following rules already published by the GTE group (19). Criteria for the diagnosis of MEN1 lesions have evolved over the study period since the first cases were registered in the fifties.…”

Section: Population and Methodsmentioning

confidence: 99%

Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d'étude des Tumeurs Endocrines

Goudet¹,

Bonithon‐Kopp²,

Murat³

et al. 2011

European Journal of Endocrinology

106

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Context: Multiple endocrine neoplasia type 1 (MEN1) disease is an autosomal dominant syndrome that is believed to equally affect men and women. This assumption has never been confirmed. Objective: The aims of this study were to evaluate the impact of gender on the prevalence of MEN1 lesions, on their lifetime probability of occurrence, and on the diagnosis of MEN1. Design: Data regarding a study of 734 cases of MEN1 from the multicenter 'Groupe d'étude des Tumeurs Endocrines' were analyzed. Results: There were 57.8% females. The prevalence and probability of pancreatic tumors were higher in males than in females (PZ0.06, PZ0.0004). This difference was due to gastrinomas. The prevalence and probability of developing pituitary tumors were significantly greater in females (P!0.001, P!0.0001). Thymic tumors were exclusively found in men. There were no significant gender differences in the prevalence and the probability of developing hyperparathyroidism, or adrenal and bronchial tumors, or in the proportion of positive genetic tests. A family history of MEN1 was more frequently found in men than in women at the time of diagnosis (PZ0.02). In the case of pituitary tumor, the proportion of patients diagnosed with MEN1 at the time of the first lesion was lower in women (44.2%) than in men (67.3%). Conclusion: The phenotype expression of the MEN1 disease gene was different in males and females. In female patients, the possibility of MEN1 is not sufficiently taken into account. Any patient presenting a lesion that belongs to the MEN1 spectrum, such as a pituitary tumor, should be closely questioned about their family history and should be tested for hypercalcemia.European Journal of Endocrinology 165 97-105

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Section: Population and Methodsmentioning

confidence: 99%

Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d'étude des Tumeurs Endocrines

Goudet¹,

Bonithon‐Kopp²,

Murat³

et al. 2011

European Journal of Endocrinology

106

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“…They have a low tendency to grow; however, 60-70% are malignant at initial manifestation , Goudet et al 2010. Resection of the primary tumor should be anticipated in all patients suitable for surgery, as it was shown to improve prognosis in both, sporadic and hereditary cases due to lower rate of LM when compared with conservatively managed patients (Norton et al 2006).…”

Section: Gastrinomasmentioning

confidence: 99%

Neuroendocrine tumor disease: an evolving landscape

Frilling

Åkerström

Falconi

et al. 2012

Endocrine-Related Cancer

149

106

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Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a heterogenous group of tumors arising from a variety of neuroendocrine cell types. The incidence and prevalence of GEPNENs have markedly increased over the last three decades. Symptoms are often absent in early disease, or vague and nonspecific even in advanced disease. Delayed diagnosis is thus common. Chromogranin A is the most commonly used biomarker but has limitations as does the proliferative marker Ki-67%, which is often used for tumor grading and determination of therapy. The development of a multidimensional prognostic nomogram may be valuable in predicting tumor behavior and guiding therapy but requires validation. Identification of NENs that express somatostatin receptors (SSTR) allows for SSTR scintigraphy and positron emission tomography imaging using novel radiolabeled compounds. Complete surgical resection of limited disease or endoscopic ablation of small lesions localized in stomach or rectum can provide cure; however, the majority of GEP-NENs are metastatic (most frequently the liver and/or mesenteric lymph nodes) at diagnosis. Selected patients with metastatic disease may benefit from advanced surgical techniques including hepatic resection or liver transplantation. Somatostatin analogs are effective for symptomatic treatment and exhibit some degree of antiproliferative activity in small intestinal NENs. There is a place for streptozotocin, temozolomide, and capecitabine in the management of pancreatic NENs, while new agents targeting either mTOR (everolimus) or angiogenic (sunitinib) pathways have shown efficacy in these lesions.

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“…There were no major differences in terms of lesion prevalence compared with the independent German and Netherlands cohorts (18,24). The GTE cohort had a median follow-up of 47 years and thus allowed us to study the age-dependent expressivity of MEN1 disease with time-to-event techniques (4,19). During this analysis, we showed intrafamilial correlations without direct phenotype-genotype correlations.…”

Section: Discussionmentioning

confidence: 82%

“…The tumors mainly develop from endocrine tissues and may arise from parathyroid glands (90-100%), the pancreas (50-70%), pituitary gland (20-40%), and adrenal glands (20-40%), and at a lower frequency from the bronchi and thymus (!15%) (2,3). Survival is limited in approximately 60% of patients because of MEN1 disease evolution (4). More than half of MEN1-related deaths are associated with tumors that are difficult to diagnose (5).…”

Section: Introductionmentioning

confidence: 99%

Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study

Thévenon

Bourredjem

Faivre

et al. 2015

European Journal of Endocrinology

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Background: MEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'é tude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1. Methods: The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. Results: Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (S.E.M.Z0.13; P!0.001) for pituitary tumor, 65% (S.E.M.Z0.21; P!0.001) for adrenal tumors, and 97% (S.E.M.Z0.41; PZ0.006) for thNETs.Conclusion: The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.

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Risk Factors and Causes of Death in MEN1 Disease. A GTE (Groupe d’Etude des Tumeurs Endocrines) Cohort Study Among 758 Patients

Cited by 303 publications

References 45 publications

Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d'étude des Tumeurs Endocrines

Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d'étude des Tumeurs Endocrines

Neuroendocrine tumor disease: an evolving landscape

Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study

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