TNF superfamily gene polymorphism as prognostic factor in early breast cancer

J Cancer Res Clin Oncol. 2010 May;136(5):685-94. doi: 10.1007/s00432-009-0707-0. Epub 2009 Nov 5.

Abstract

Purpose: Since apoptosis may play a role in the prognosis of breast cancer, the present study analyzed the polymorphisms of apoptosis-related genes and their impact on the survival of 240 patients with early invasive ductal breast cancer.

Methods: The genomic DNA was extracted from paraffin-embedded tumor-free tissue or blood, and 12 single nucleotide polymorphisms (SNPs) of 11 apoptosis-related genes in the apoptosis pathway determined using a Sequenom MassARRAY system.

Results: During the median follow-up of 53.4 (range 2.9-205.9) months, 37 relapses and 22 deaths occurred. Among the target polymorphisms, the tumor necrosis factor superfamily member 10 gene polymorphism (TNFSF10 rs1131532) in a recessive model of the T allele and prostaglandin-endoperoxide synthase 2 gene polymorphism (PTGS2 rs5275) in a dominant model of the C allele were associated with survival in a log-rank test. The TT genotype of TNFSF10 (rs1131532) was also significantly correlated with a lower disease-free, distant disease-free, and overall survival in a multivariate analysis (HR = 3.304, 4.757, and 6.459; P = 0.002, 0.001, and 0.009, respectively), while PTGS2 rs5275 was only associated with a higher distant disease-free survival (HR = 0.302; P = 0.041). No clinicopathologic difference was observed according to the genotypes of these two polymorphisms.

Conclusion: The TNFSF10 (rs1131532) polymorphism was identified as a possible prognostic factor of survival in patients with operated invasive breast cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal / genetics*
  • Carcinoma, Ductal / mortality
  • Carcinoma, Ductal / pathology
  • Cyclooxygenase 2 / genetics
  • Female
  • Humans
  • Middle Aged
  • Prognosis
  • TNF-Related Apoptosis-Inducing Ligand / genetics
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Biomarkers, Tumor
  • TNF protein, human
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Cyclooxygenase 2