FOXP3 Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes

Dis Markers. 2017:2017:6359603. doi: 10.1155/2017/6359603. Epub 2017 Jun 21.

Abstract

FOXP3 genetic polymorphisms have been associated with cancer development and prognosis. In this context, the present study aimed to evaluate the g.10403A>G (rs2232365) polymorphisms and g.8048A>C (rs3761548), in aggressive breast cancer (BC) subtypes, including, Luminal B HER2+ (LB), HER2-enriched (HER2+), and triple-negative (TN). Polymerase chain reaction followed by enzymatic restriction was performed to genotyping 117 BC samples and 300 controls. A significant association of AA genotype (g.10403A>G) in relation to BC susceptibility (OR = 1.93; 95% CI = 1.01-3.66; p = 0.046) was observed. The GG (g.10403A>G) genotype was correlated with higher proliferation index (Ki-67) in HER2+ subtype (τ = 0.47; p = 0.019) and advanced TNM staging in TN (τ = 0.23; p = 0.032). A correlation of AA genotype (g.8048A>C) with higher Ki-67 (τ = -0.47; p = 0.018) and lower histological grade (τ = 0.39; p = 0.026) in HER2+ was also found. GA haplotype was correlated with lower histological grade (τ = -0.15; p = 0.009) and higher Ki-67 (τ = 0.43; p = 0.036) in HER2+ and advanced staging in TN (τ = 0.29; p = 0.044). On the other hand, AC haplotype was correlated with lower Ki-67 (τ = -0.54; p = 0.005) and staging (τ = -0.29; p = 0.027) in HER2+ and TN respectively. Results showed that FOXP3 influence regarding clinical outcome depends greatly on the BC subtype and indicated this transcription factor as a promising marker in aggressive BC subtypes.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Female
  • Forkhead Transcription Factors / genetics*
  • Haplotypes
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptor, ErbB-2 / genetics

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • ERBB2 protein, human
  • Receptor, ErbB-2