RESUMO
BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.
Assuntos
Esôfago de Barrett/genética , Proteínas Morfogenéticas Ósseas/genética , Predisposição Genética para Doença , Fatores de Diferenciação de Crescimento/genética , Polimorfismo de Nucleotídeo Único , Proteínas com Domínio T/genética , Esôfago de Barrett/etiologia , Neoplasias Esofágicas/genética , Estudo de Associação Genômica Ampla , Humanos , RiscoRESUMO
AIM: To present a critical discussion of the efficacy of the faecal pyruvate kinase isoenzyme type M2 (faecal M2-PK) test for colorectal cancer (CRC) screening based on the currently available studies. METHODS: A literature search in PubMed and Embase was conducted using the following search terms: fecal Tumor M2-PK, faecal Tumour M2-PK, fecal M2-PK, faecal M2-PK, fecal pyruvate kinase, faecal pyruvate kinase, pyruvate kinase stool and M2-PK stool. RESULTS: Stool samples from 704 patients with CRC and from 11 412 healthy subjects have been investigated for faecal M2-PK concentrations in seventeen independent studies. The mean faecal M2-PK sensitivity was 80.3%; the specificity was 95.2%. Four studies compared faecal M2-PK head-to-head with guaiac-based faecal occult blood test (gFOBT). Faecal M2-PK demonstrated a sensitivity of 81.1%, whereas the gFOBT detected only 36.9% of the CRCs. Eight independent studies investigated the sensitivity of faecal M2-PK for adenoma (n = 554), with the following sensitivities: adenoma < 1 cm in diameter: 25%; adenoma > 1 cm: 44%; adenoma of unspecified diameter: 51%. In a direct comparison with gFOBT of adenoma > 1 cm in diameter, 47% tested positive with the faecal M2-PK test, whereas the gFOBT detected only 27%. CONCLUSION: We recommend faecal M2-PK as a routine test for CRC screening. Faecal M2-PK closes a gap in clinical practice because it detects bleeding and non-bleeding tumors and adenoma with high sensitivity and specificity.
