RESUMEN
The G allele of the rs6983267 single-nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer (TC) has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in TC susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3067 cases and 8575 controls. We detected significant associations between rs6983267G and TC in the British Isles (odds ratio (OR)=1.19, 95% CI: 1.11-1.27, P=4.03×10(-7)), Japan (OR=1.20, 95% CI: 1.03-1.41, P=0.022) and a borderline significant association of similar effect direction and size in Colombia (OR=1.19, 95% CI: 0.99-1.44, P=0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5484 cases and 12â594 controls, confirmed the association between rs6983267G and TC (P=1.23×10(-7), OR=1.13, 95% CI: 1.08-1.18). Our results therefore support the notion that rs6983267G is a bona fide TC risk variant that increases the risk of disease by â¼13%.
Asunto(s)
Cromosomas Humanos Par 8/genética , Sitios Genéticos , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/genética , Estudios de Casos y Controles , Colombia/epidemiología , Humanos , Japón/epidemiología , Metaanálisis como Asunto , Pronóstico , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
Thyroid cancer in children is usually rare, but in the individuals exposed to radiation risk of disease increases considerably. After the Chernobyl accident in 1986, an over 10-fold maximal elevation in the incidence of thyroid cancer was registered about a decade later, cumulatively resulting in more than a thousand of newly diagnosed cases in children who lived in the territories of Belarus, Russia, and Ukraine affected by radioactive fallouts. Experience from the epidemic substantially promoted knowledge in clinical pediatric oncology, pathology and basic sciences. This article overviews epidemiology, clinical features, results of treatment and follow-up of childhood patients with radiation-induced Chernobyl thyroid cancer in comparison to sporadic cases diagnosed at present. In addition, we discuss general issues of pathology and molecular findings in childhood thyroid carcinomas.
Asunto(s)
Carcinoma , Accidente Nuclear de Chernóbil , Neoplasias Inducidas por Radiación , Neoplasias de la Tiroides , Adolescente , Distribución por Edad , Carcinoma/epidemiología , Carcinoma/genética , Carcinoma/patología , Carcinoma/terapia , Niño , Preescolar , Europa Oriental/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/genética , Neoplasias Inducidas por Radiación/patología , Neoplasias Inducidas por Radiación/terapia , Liberación de Radiactividad Peligrosa , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapiaRESUMEN
Apoptosis is an essential physiological process of elimination of destined cells during the development and differentiation or after damage from external stresses such as ionizing radiation or chemotherapeutic agents. Disruption of apoptosis is proved to cause various diseases including cancer. Among numerous molecules involved in diverse anti- or pro-apoptotic signaling pathways, NF-kappaB is one of the key factors controlling anti-apoptotic responses. Its anti-apoptotic effect is thought to be mediated through not only transcriptional activation of dependent genes but also by crosstalking with the JNK pathway. Oncogenic proteins such as Ret/PTC, Ras and BRAF can induce NF-kappaB activation making it an important change in thyroid cancer. A number of specific or non-specific NF-kappaB inhibitors have been tried to take over the cascade in in vitro and in vivo experiments. These agents can induce massive apoptosis especially in combination with radio- or chemotherapy. Current results suggest that the inhibition of the NF-kappaB may be a promising strategy for advanced thyroid cancer treatment but further investigations are warranted to develop specific and clinically effective NF-kappaB inhibitors in future.
Asunto(s)
Apoptosis/fisiología , Carcinoma/tratamiento farmacológico , FN-kappa B/fisiología , Neoplasias de la Tiroides/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Benzamidas/metabolismo , Benzamidas/farmacología , Carcinoma/metabolismo , Ciclohexanonas/metabolismo , Ciclohexanonas/farmacología , Activación Enzimática , Humanos , Proteínas Inhibidoras de la Apoptosis/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Transducción de Señal/genética , Neoplasias de la Tiroides/metabolismo , Activación Transcripcional/genéticaRESUMEN
Thyroid cancer in children is usually rare, but in the individuals exposed to radiation risk of disease increases considerably. After the Chernobyl accident in 1986, an over 10-fold maximal elevation in the incidence of thyroid cancer was registered about a decade later, cumulatively resulting in more than a thousand of newly diagnosed cases in children who lived in the territories of Belarus, Russia, and Ukraine affected by radioactive fallouts. Experience from the epidemic substantially promoted knowledge in clinical pediatric oncology, pathology and basic sciences. This article overviews epidemiology, clinical features, results of treatment and follow-up of childhood patients with radiation-induced Chernobyl thyroid cancer in comparison to sporadic cases diagnosed at present. In addition, we discuss general issues of pathology and molecular findings in childhood thyroid carcinomas.
O câncer de tiróide é habitualmente raro em crianças, mas em indivíduos expostos a radiação o risco da doença aumenta consideravelmente. Cerca de uma década após o acidente de Chernobil, em 1986, foi registrado um aumento de mais de 10 vezes na incidência de câncer de tiróide, resultando cumulativamente em mais de mil novos casos diagnosticados em crianças que viviam nos territórios da Bielorrússia, Russia, e Ucrânia, afetadas pela chuva radioativa. A experiência com essa epidemia resultou em conhecimento substancial de oncologia pediátrica clínica, patologia e ciências básicas. Este artigo analisa a epidemiologia, os achados clínicos, os resultados do tratamento e a evolução de pacientes pediátricos com câncer de tiróide induzido pela radiação de Chernobil, em comparação com casos esporádicos diagnosticados atualmente. Adicionalmente, serão discutidos tópicos de patologia e achados moleculares no carcinoma de tiróide infantil.
Asunto(s)
Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Carcinoma , Accidente Nuclear de Chernóbil , Neoplasias Inducidas por Radiación , Neoplasias de la Tiroides , Distribución por Edad , Carcinoma/epidemiología , Carcinoma/genética , Carcinoma/patología , Carcinoma/terapia , Europa Oriental/epidemiología , Incidencia , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/genética , Neoplasias Inducidas por Radiación/patología , Neoplasias Inducidas por Radiación/terapia , Liberación de Radiactividad Peligrosa , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapiaRESUMEN
Apoptosis is an essential physiological process of elimination of destined cells during the development and differentiation or after damage from external stresses such as ionizing radiation or chemotherapeutic agents. Disruption of apoptosis is proved to cause various diseases including cancer. Among numerous molecules involved in diverse anti- or pro-apoptotic signaling pathways, NF-kappaB is one of the key factors controlling anti-apoptotic responses. Its anti-apoptotic effect is thought to be mediated through not only transcriptional activation of dependent genes but also by crosstalking with the JNK pathway. Oncogenic proteins such as Ret/PTC, Ras and BRAF can induce NF-kappaB activation making it an important change in thyroid cancer. A number of specific or non-specific NF-kappaB inhibitors have been tried to take over the cascade in in vitro and in vivo experiments. These agents can induce massive apoptosis especially in combination with radio- or chemotherapy. Current results suggest that the inhibition of the NF-kappaB may be a promising strategy for advanced thyroid cancer treatment but further investigations are warranted to develop specific and clinically effective NF-kappaB inhibitors in future.
A apoptose é um processo fisiológico essencial destinado a eliminar células durante o desenvolvimento e diferenciação ou após danos decorrentes de estresses externos com a radiação ionizante ou agentes quimioterápicos. Distúrbios na apoptose têm sido demonstrados como causadores de várias doenças, incluindo câncer. Entre as inúmeras moléculas envolvidas nas várias vias de sinalização anti- ou pró-apoptoticas, NF-kapaB é um dos fatores-chave que controlam as respostas anti-apoptóticas. Acredita-se que seu efeito anti-apoptótico seja mediado não apenas pela ativação transcricional de genes dependentes mas também por crosstalking com a via JNK. Proteínas oncogênicas como Ret/PTC, Ras e BRAF podem induzir ativação de NF-kapaB promovendo importante transformação no câncer da tireóide. Uma série de inibidores específicos e não-específicos do NF-kapaB tem sido usada em experimentos in vitro e in vivo procurando inibir a cascata. Esses agentes podem induzir apoptose maciça especialmente em combinação com radio ou quimioterapia. Resultados atuais sugerem que a inibição de NF-kapaB pode ser uma estratégia promissora no tratamento do câncer da tireóide avançado, mas novas investigações são necessárias para desenvolver inibidores específicos e clinicamente efetivos do NF-kapaB.