RESUMO
The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with Pcombined<3 × 10-8): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR=1.20, P=3.2 × 10-7) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer.
Assuntos
Carcinoma Papilar/genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Neoplasias da Glândula Tireoide/genética , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , Cromossomos Humanos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Frequência do Gene/genética , Predisposição Genética para Doença , Variação Estrutural do Genoma , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Hormônios Hipofisários/análise , Fatores de Risco , Câncer Papilífero da Tireoide , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , População Branca/genética , Sequenciamento Completo do GenomaRESUMO
The most common causes of mediastinal masses are thymomas, lymphomas and neuromas. Mediastinal cysts, such as bronchogenic cysts, which are usually benign, are less common. We report the case of a 59-year-old woman with a history of progressive dysphagia. A computed tomography scan revealed a cystic lesion in the anterior mediastinum. The cyst was surgically resected and turned out to be a benign parathyroid cyst. The patient's symptoms disappeared after surgical removal. Both the serum calcium and parathyroid hormone levels were normal before, and after surgery. Parathyroid cysts are rare lesions of the mediastinum and only around 100 cases have been reported in literature. Here we report the first case of a mediastinal parathyroid cyst in Iceland.
Assuntos
Cisto Mediastínico , Doenças das Paratireoides , Biópsia , Transtornos de Deglutição/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Cisto Mediastínico/complicações , Cisto Mediastínico/diagnóstico , Cisto Mediastínico/cirurgia , Pessoa de Meia-Idade , Doenças das Paratireoides/complicações , Doenças das Paratireoides/diagnóstico , Doenças das Paratireoides/cirurgia , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: In late 2007, the availability of immediate breast reconstructions increased as a result of the establishment of an oncoplastic breast surgical service at Landspítali-The National University Hospital The aim of this study was to look at the rates and early complications of immediate breast reconstructions in our hospital in 2008-2010 and compare with the results from the UK National Mastectomy and Breast Reconstruction Audit (NMBRA). MATERIAL AND METHODS: This is a retrospective population-based study, including all women who had immediate breast reconstruction at Landspítali in 2008-2010. RESULTS: 319 mastectomies and 157 breast reconstructions were performed. Of these, 98 (62%) were immediate, (mean age 49, 29-69). The immediate breast reconstruction rate was therefore 31%, with a respective 55% for patients 50 years old or younger. In comparison, the rate was 5% in 2000-2005. Immediate reconstructions with an extended autologous latissimus dorsi flap were performed in 25 (26%) cases and implant based reconstructions in the remaining (n=73, 74%). Inpatient complications occurred in 12 (12%) patients and 5 needed reoperation (3 post-operative bleeding, 1 skin necrosis, 1 imminent LD-flap failure). Readmission due to complications after discharge occurred in 14 (14%), while 37 (38%) developed mild complications not requiring readmission. The results were comparable to NMBRA, although the rates of autologous flap reconstructions were significantly higher than in this study (63% vs. 26%). CONCLUSION: As a result of the establishment of an oncoplastic breast surgical service at Landspítali, the rates of immediate breast reconstruction have increased significantly (from 5% to 31%). The complication rates are low and similar to NMBRA.
Assuntos
Implante Mamário , Neoplasias da Mama/cirurgia , Hospitais Universitários , Mamoplastia/métodos , Mastectomia , Retalhos Cirúrgicos , Adulto , Idoso , Implante Mamário/efeitos adversos , Feminino , Humanos , Islândia , Mamoplastia/efeitos adversos , Auditoria Médica , Pessoa de Meia-Idade , Readmissão do Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Reoperação , Estudos Retrospectivos , Retalhos Cirúrgicos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Reino UnidoRESUMO
To search for sequence variants conferring risk of nonmedullary thyroid cancer, we focused our analysis on 22 SNPs with a P < 5 × 10(-8) in a genome-wide association study on levels of thyroid stimulating hormone (TSH) in 27,758 Icelanders. Of those, rs965513 has previously been shown to associate with thyroid cancer. The remaining 21 SNPs were genotyped in 561 Icelandic individuals with thyroid cancer (cases) and up to 40,013 controls. Variants suggestively associated with thyroid cancer (P < 0.05) were genotyped in an additional 595 non-Icelandic cases and 2,604 controls. After combining the results, three variants were shown to associate with thyroid cancer: rs966423 on 2q35 (OR = 1.34; P(combined) = 1.3 × 10(-9)), rs2439302 on 8p12 (OR = 1.36; P(combined) = 2.0 × 10(-9)) and rs116909374 on 14q13.3 (OR = 2.09; P(combined) = 4.6 × 10(-11)), a region previously reported to contain an uncorrelated variant conferring risk of thyroid cancer. A strong association (P = 9.1 × 10(-91)) was observed between rs2439302 on 8p12 and expression of NRG1, which encodes the signaling protein neuregulin 1, in blood.
Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 2/genética , Cromossomos Humanos Par 8/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Neoplasias da Glândula Tireoide/genética , Tireotropina/metabolismo , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Islândia , Neuregulina-1/sangue , Neuregulina-1/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
In order to search for sequence variants conferring risk of thyroid cancer we conducted a genome-wide association study in 192 and 37,196 Icelandic cases and controls, respectively, followed by a replication study in individuals of European descent. Here we show that two common variants, located on 9q22.33 and 14q13.3, are associated with the disease. Overall, the strongest association signals were observed for rs965513 on 9q22.33 (OR = 1.75; P = 1.7 x 10(-27)) and rs944289 on 14q13.3 (OR = 1.37; P = 2.0 x 10(-9)). The gene nearest to the 9q22.33 locus is FOXE1 (TTF2) and NKX2-1 (TTF1) is among the genes located at the 14q13.3 locus. Both variants contribute to an increased risk of both papillary and follicular thyroid cancer. Approximately 3.7% of individuals are homozygous for both variants, and their estimated risk of thyroid cancer is 5.7-fold greater than that of noncarriers. In a study on a large sample set from the general population, both risk alleles are associated with low concentrations of thyroid stimulating hormone (TSH), and the 9q22.33 allele is associated with low concentration of thyroxin (T(4)) and high concentration of triiodothyronine (T(3)).