CCR2-V64I genetic polymorphism: a possible involvement in HER2+ breast cancer

Clin Exp Med. 2016 May;16(2):139-45. doi: 10.1007/s10238-015-0342-9. Epub 2015 Feb 26.

Abstract

Many tumor cells express chemokines and chemokine receptors, and these molecules can affect both tumor progression and anti-tumor immune response. Genetic polymorphisms of some chemokine receptors were found to be closely related to malignant tumors, especially in metastasis process, including breast cancer (BC). Considering this, it was investigated a possible role for CCR2-V64I (C-C chemokine receptor 2) and CCR5-Δ32 (C-C chemokine receptor 5) genetic variants in BC context. Patients were divided into subgroups according to immunohistochemical profile of estrogen (ER) and progesterone (PR) receptors and the human epidermal growth factor receptor 2 (HER2) overexpression. No significant associations were found in relation to susceptibility (CCR2-V64I: OR 1.32; 95 % CI 0.57-3.06; CCR5-∆32: OR 1.04; 95 % CI 0.60-1.81), clinical outcome (tumor size, lymph nodes commitment and/or distant metastasis, TNM staging and nuclear grade) or therapeutic response (recurrence and survival). However, it was found a significant correlation between CCR2-V64I allelic variant and HER2 immunohistochemical positive samples (p = 0.026). All in all, we demonstrate, for the first time, a positive correlation between CCR2 receptor gene polymorphism and a subgroup of BC related to poor prognosis, which deserves further investigation in larger samples for validation.

Keywords: Breast cancer; CCR2; Clinical outcome; Genetic polymorphism; HER2.

Publication types

  • Review

MeSH terms

  • Amino Acid Substitution*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Immunohistochemistry
  • Mutant Proteins / genetics
  • Prognosis
  • Receptor, ErbB-2 / genetics*
  • Receptors, CCR2 / genetics*

Substances

  • CCR2 protein, human
  • Mutant Proteins
  • Receptors, CCR2
  • ERBB2 protein, human
  • Receptor, ErbB-2