RESUMO
Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).
Assuntos
Moléculas de Adesão Celular/genética , Café/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A2/genética , Ingestão de Líquidos/genética , Estudo de Associação Genômica Ampla/métodos , Antígenos de Neoplasias/genética , Proteínas Reguladoras de Apoptose/genética , Cafeína/farmacologia , Linhagem Celular , Feminino , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença/genética , Humanos , Masculino , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , População Branca/genéticaRESUMO
In 4 patients, an incidentaloma of the thyroid was found on 18-fluoro-deoxyglucose positron-emission tomography (FDG-PET). In the first patient, a 73-year-old man, a medullary thyroid carcinoma was discovered during the staging procedure ofa laryngeal carcinoma. In the second patient, an 81-year-old woman, a follicular thyroid carcinoma was found as a result of a FDG-PET evaluation of an adenocarcinoma of the lung. In the third patient, a 64-year-old woman, a papillary thyroid carcinoma was found during dissemination investigation after curative removal of an adrenocortical carcinoma. The last patient, a 78-year-old man, was found to have a thyroid incidentaloma on FDG-PET scan during staging ofa recurrence of a gastrointestinal stromal tumour. Thyroid incidentalomas are present on 1.2-2.3% of FDG-PET scans. Further diagnostic work-up of these lesions by fine needle aspiration is warranted since up to 50% are malignant. However, whether these malignant thyroid lesions are relevant is not always clear. Treatment depends on the primary disease for which the FDG-PET scan was initially made. This requires good evaluation and discussion with the patient.
