The impact of renin-angiotensin system, angiotensin І converting enzyme (insertion/deletion), and angiotensin ІІ type 1 receptor (A1166C) polymorphisms on breast cancer survival in Iran.
BACKGROUND
Several proteins of renin-angiotensin system (RAS) have been implicated in the process of growth promotion or inhibition of breast tissue and cancer cells. This study aimed to investigate the association between angiotensin I converting enzyme (ACE) insertion/deletion (I/D) and angiotensin receptor-1 (AGTR1) A1166C polymorphisms and survival of 110 women with breast cancer.


METHODS
The I/D and A1166C polymorphisms were evaluated by using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) in 110 breast cancer patients who had been treated between 2007 and 2009. Genomic DNA was extracted from a Formalin-Fixed Paraffin-Embedded (FFPE) tissue of breast cancer sample blocks. All the potential clinical and pathological prognostic variables were analyzed to establish the impact of I/D and A1166C polymorphisms on disease-free and overall survival rates. Disease-free and overall survival rates were the primary endpoints of the study.


RESULTS
The ACE (I/D) polymorphism was associated with 3-year disease-free survival. Disease-free survival in DD carriers was significantly increased compared to ID plus II carriers (HR=4.75; 95% CI, 1.39-16.24; p=0.013). No significant association was found between AGTR1 (A1166C) and 3-year disease-free survival (p=0.233). Also, the ACE (I/D) and AGTR1 (A1166C) polymorphisms were not associated with breast cancer overall survival.


CONCLUSIONS
The ACE (I/D) polymorphism was associated with 3-year disease-free survival of the women with breast cancer. Besides, disease-free survival in DD carriers was significantly increased compared to ID plus II carriers.
Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Soha
S
Namazi
Arghavan
A
Daneshian
Mohammad
M
Mohammadianpanah
Peyman
P
Jafari
Shirin
S
Ardeshir-Rouhani-Fard
Shiva
S
Nasirabadi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007492:Iran; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D017384:Sequence Deletion; D055815:Young Adult
D044140:Receptor, Angiotensin, Type 1; D007703:Peptidyl-Dipeptidase A
A/C; ACE; AGTR1; AGTR1(A1166C); Ang-(1–7); Disease-free survival; ER; FFPE; Formalin-Fixed Paraffin-Embedded; GST; HER-2; I/D; NEP; Overall survival; PCR; POP; PR; Polymerase Chain Reaction; Polymorphism; RAS; RFLP; Renin–angiotensin system; Restriction Fragment Length Polymorphism; SNP; SPSS; Statistical Package for Social Sciences; TNM; TOP; VEGF; adenine/cytosine; angiotensin I converting enzyme; angiotensin receptor-1; angiotensin-(1–7); estrogen receptor; glutathione-S-transferase; human epidermal growth factor receptor 2; insertion/deletion; neprilysin; progesterone receptor; prolyl-oligopeptidase; renin–angiotensin system; single nucleotide polymorphism; thimet-oligopeptidase; tumor, node, metastasis; vascular endothelial growth factor