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1.
Int J Mol Sci ; 17(5)2016 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-27136531

RESUMO

Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Metastasis remains the primary cause of CRC death. Predicting the possibility of metastatic relapse in early-stage CRC is of paramount importance to target therapy for patients who really need it and spare those with low-potential of metastasis. Ninety-six stage II CRC cases were stratified using high-resolution array comparative genomic hybridization (aCGH) data based on a predictive survival algorithm and supervised clustering. All genes included within the resultant copy number aberrations were each interrogated independently at mRNA level using CRC expression datasets available from public repositories, which included 1820 colon cancers, and 167 normal colon tissues. Reduced mRNA expression driven by copy number losses and increased expression driven by copy number gains revealed 42 altered transcripts (29 reduced and 13 increased transcripts) associated with metastatic relapse, short disease-free or overall survival, and/or epithelial to mesenchymal transition (EMT). Resultant genes were classified based on gene ontology (GO), which identified four functional enrichment groups involved in growth regulation, genomic integrity, metabolism, and signal transduction pathways. The identified 42 genes may be useful for predicting metastatic relapse in stage II CRC. Further studies are necessary to validate these findings.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Idoso , Algoritmos , Aberrações Cromossômicas , Análise por Conglomerados , Neoplasias Colorretais/mortalidade , Hibridização Genômica Comparativa , Bases de Dados Genéticas , Transição Epitelial-Mesenquimal , Feminino , Humanos , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Taxa de Sobrevida
2.
Sci Rep ; 9(1): 19071, 2019 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836807

RESUMO

Obesity is a well-known risk factor for multiple diseases including multiple sclerosis (MS). Polymorphisms in the fat-mass obesity (FTO) gene have been consistently found to be associated with obesity, and recently found to increase the risk of developing MS. We therefore assessed the common FTO gene polymorphism (rs9939609) in relation to obesity, risk of developing MS and its disability in a cohort of MS patients. A cohort of 200 MS patients (135 females and 65 males) were genotyped for the FTO rs9939609 polymorphism. Using both logistic and linear regression we assessed the relationship between the variant and the selected phenotypes under both an additive and recessive genetic models. The A-allele was found to be associated with being overweight/obese in MS patients (OR = 2.48 (95% CI 1.17-5.29); p = 0.01). In addition, The A-allele was also found to be associated with increased MS disability (ß = 0.48 (95% CI 0.03-0.92); p = 0.03). However, no association was found with risk of developing MS (p > 0.05). Moreover, our association with obesity is consistent with previous reports, whereas the association with disability is novel and warrants further investigation on the role of FTO in disease progression.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Avaliação da Deficiência , Estudos de Associação Genética , Predisposição Genética para Doença , Esclerose Múltipla/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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