Association between the polymorphisms of angiotensin converting enzyme (Peptidyl-Dipeptidase A) INDEL mutation (I/D) and Angiotensin II type I receptor (A1166C) and breast cancer among post menopausal Egyptian females

Abstract

Renin angiotensin system (RAS) is involved in the regulation of cardiovascular homeostasis. Angiotensin (Ang II) is converted from angiotensin I via angiotensin converting enzyme (ACE). Ang II exerts its effects by binding to two types of receptors; AT1R and AT2R. Ang II effect on AT1R promotes proliferation, angiogenesis and metastasis in breast tissues. ACE (I/D) polymorphism is an insertion/deletion of a 287 bp DNA fragment within intron 16 of ACE gene. A1166C is a single nucleotide polymorphism (SNP) in the 30-UTR of AT1R gene. Both (D) and (C) alleles were found to be related to RAS overactivation.
Subjects and methods: One hundred and twenty postmenopausal Egyptian females were included in the present study and were divided into control group (fifty apparently healthy women) and patients group (seventy breast cancer patients). Detailed history taking was done with stress on age, family history, menstrual, obstetric, medical and drug history. Physical examination including body mass index calculation was done. Histopathological examination was done for tumor grading and staging. Detection of ACE gene (I/D) polymorphism by PCR and AT1R A1166C SNP using PCR/RFLP were done. 
Results: A statistically significant difference in AT1R A1166C SNP genotype frequencies was found among the studied groups. The patients group showed higher frequency of ‘‘CC’’ (2.9% vs 0%) and ‘‘AC’’ (44.3% vs 24%) and lower frequency of ‘‘AA’’ genotype (52.9% vs 76%) than controls. The patients also showed significant higher frequency of allele ‘‘C’’ (25% vs 12%) which was associated with increased breast cancer risk with an Odds ratio of 2.4444 (95% CI: 1.1967– 4.9931). Testing the dominant model of inheritance revealed a statistically higher frequency of exposed genotypes ‘‘AC and CC’’ among the patients group (47.1% vs 24%, respectively; p= 0.013) with substantial increase in breast cancer risk among the exposed genotypes with an Odds ratio of 2.8243 (95% CI: 1.2679–6.2913). The present study demonstrated that (AC and CC) genotypes of AT1R A1166C SNP and increased BMI can be considered as predictors for breast cancer risk among post menopausal Egyptian females. Results also revealed that A1166C SNP of AT1R gene and ACE/ID polymorphism could not be considered as predictors for breast cancer prognosis.

KEYWORDS Breast neoplasm; INDEL mutation; Renin-angiotensin system; Peptidyl-Dipeptidase A