Association of angiotensin I converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms with breast cancer prognostic factors in Iranian population

Mol Carcinog. 2010 Dec;49(12):1022-30. doi: 10.1002/mc.20685.


It has been indicated that renin-angiotensin system (RAS) has role in various steps of cancer progression. The presence of RAS components has been shown in normal and breast cancer tissue. insertion/deletion (I/D) is one of angiotensin I converting enzyme (ACE) polymorphisms and A1166C is one of angiotensin II type-1 receptor (AT1R) polymorphisms which have been associated with various diseases such as cardiovascular diseases. In the present study, we aimed to substantiate the putative significance of ACE and AT1R on breast cancer biology by investigating the influence of their gene polymorphisms on breast cancer progression. The I/D and A1166C polymorphisms were evaluated by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), respectively in 70 breast cancer patients diagnosed with invasive breast cancer and 70 healthy women. Breast cancer prognostic factors were obtained from medical and pathology reports of patients. There was no significant difference between cases and controls for ACE (I/D) (P = 0.15) and AT1R (A1166C) genotypes (P = 0.86). In breast cancer patients, when DD genotype was used as reference group, the combination of II and ID genotypes was associated with increased HER-2 expression (P = 0.020; OR, 4.58; 95% CI, 1.26-16.60). Also, when AA genotype was used as reference group, the AC genotype was associated with higher tumor TNM stage (P = 0.024; OR, 4.66; 95% CI, 1.18-18.35). This is the first study indicating that ACE (I/D) polymorphism is associated with HER-2 expression and AT1R (A1166C) polymorphism is associated with tumor TNM stage in breast cancer patients.

MeSH terms

  • Adult
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genotype
  • Humans
  • Iran
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic*
  • Prognosis
  • Receptor, Angiotensin, Type 1 / genetics*
  • Receptor, ErbB-2 / genetics


  • Receptor, Angiotensin, Type 1
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Peptidyl-Dipeptidase A