Mutation in CNR1 gene and VEGF expression in esophageal cancer.
OBJECTIVE
Cannabinoid receptors have an impact on gastrointestinal function, but it remains unknown whether mutations may affect tumor susceptibility in patients with esophageal carcinoma. The aim of this study was to determine mutation in the cannabinoid receptor-1 (CNR1) gene and its relation to vascular endothelial growth factor (VEGF) expression as an angiogenic and poor prognostic factor.


METHODS
179 esophageal tissue samples from 69 patients (29 with esophageal cancer and 40 controls) were studied. CNR1 gene mutation (1359 G --> A in codon 453) was detected with PCR, using the MspI restriction enzyme. VEGF was determined by immunoassay.


RESULTS
Genotyping in control patients' samples revealed that 24/40 were G/G wild type and 16/40 were G/A; no samples were A/A. Of the 139 tissue samples from the 29 esophageal cancer patients, 15 were G/G homozygous, 85 G/A heterozygous, 11 had an A/A genotype and 28 were without amplification. In the normal tissue adjacent to tumor, some mutations were observed. The overall survival time was reduced in patients with the A/A type in all their 5 samples, in comparison to G/G type (P = 0.04, chi-square: 4.26). VEGF expression was higher in tumor than nontumor areas (P < 0.025). VEGF expression was not correlated with survival time.


CONCLUSIONS
Our preliminary findings in esophageal tissue showed a high frequency of G --> A mutation in the CNR1 gene. No correlation between VEGF expression and gene receptor mutation was found. Patients with mutation in all their samples had a reduced survival time.
Research Center, Hospital Universitario 12 de Octubre, Madrid, Spain.
Fernando
F
Bedoya
Juan C
JC
Meneu
Maria Isabel
MI
Macías
Almudena
A
Moreno
Rafael
R
Enríquez-De-Salamanca
Enrique Moreno
EM
Gonzalez
Irene
I
Vegh
D014408:Biomarkers, Tumor / Q000235:genetics; D004252:DNA Mutational Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D043884:Receptor, Cannabinoid, CB1; D042461:Vascular Endothelial Growth Factor A