<i>FOXP3</i>Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes

Abstract

<i>FOXP3</i> 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; <i>p</i> = 0.046) was observed. The GG (g.10403A>G) genotype was correlated with higher proliferation index (Ki-67) in HER2+ subtype (<i>τ</i> = 0.47; <i>p</i> = 0.019) and advanced TNM staging in TN (<i>τ</i> = 0.23; <i>p</i> = 0.032). A correlation of AA genotype (g.8048A>C) with higher Ki-67 (<i>τ</i> = -0.47; <i>p</i> = 0.018) and lower histological grade (<i>τ</i> = 0.39; <i>p</i> = 0.026) in HER2+ was also found. GA haplotype was correlated with lower histological grade (<i>τ</i> = -0.15; <i>p</i> = 0.009) and higher Ki-67 (<i>τ</i> = 0.43; <i>p</i> = 0.036) in HER2+ and advanced staging in TN (<i>τ</i> = 0.29; <i>p</i> = 0.044). On the other hand, AC haplotype was correlated with lower Ki-67 (<i>τ</i> = -0.54; <i>p</i> = 0.005) and staging (<i>τ</i> = -0.29; <i>p</i> = 0.027) in HER2+ and TN respectively. Results showed that <i>FOXP3</i> influence regarding clinical outcome depends greatly on the BC subtype and indicated this transcription factor as a promising marker in aggressive BC subtypes.