An A/C Germline Single-Nucleotide Polymorphism in the TNFAIP3 Gene Is Associated With Advanced Disease Stage and Survival in Only Surgically Treated Esophageal Cancer

J Hum Genet. 2014 Dec;59(12):661-6. doi: 10.1038/jhg.2014.90. Epub 2014 Oct 30.

Abstract

Prognostication of disease relapse and survival is essential for cancer patients and genetic variations in cancer patients may serve as important indicators. A single-nucleotide polymorphism (SNP) mapping to the tumor necrosis factor, alpha-induced protein 3 (TNFAIP3) gene at position 138241110 displays three genotypes (AA, AC and CC). The aim of this study was to evaluate the potential prognostic value of the TNFAIP3-SNP in esophageal cancer (EC). Genomic DNA was extracted from peripheral blood leukocytes of 173 patients who underwent complete surgical resection for EC and did not receive any neoadjuvant or adjuvant therapy. For SNP detection, a 260- bp fragment was PCR amplified, purified and sequenced with tested primers. The product was analyzed by automatic DNA sequencer.The TNFAIP3 genotypes were correlated with clinico-pathological parameters, tumor cell dissemination in bone marrow and clinical outcome. The C-allele carrier presented with higher disease stage (P<0.001). This was predominantly because of the presence of lymph node metastasis (P<0.001). The recurrence rate was higher in C-allele carriers (AC and CC genotype; P=0.004). Kaplan-Meier plots for disease-free (P=0.017) and overall survival (P<0.001) displayed a gene dosage-associated outcome with AA genotype patients presenting the longest and CC genotype patients the poorest survival. In disease stage-adjusted multivariate analysis the TNFAIP3-SNP was identified as an independent prognostic factor for survival (hazard ratio 1.9; P=0.008). The TNFAIP3-SNP allows risk stratification of EC patients and may be a useful tool to identify patients eligible for multimodal therapy concepts.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • DNA-Binding Proteins / genetics*
  • Disease-Free Survival
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / surgery
  • Genetic Association Studies
  • Germ-Line Mutation
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / surgery
  • Neoplasm Staging
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Prognosis*
  • Sequence Analysis, DNA
  • Tumor Necrosis Factor alpha-Induced Protein 3

Substances

  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3