Role of Angiotensin Converting Enzyme (ACE) Gene Polymorphism in Breast Cancer among North Indian Population

ABSTRACT

Background: The most common cause of cancer related death among women in the world is Breast cancer (BCa). Almost Every year, approximately 1,300,000 cases and 450,000 deaths are related with Carcinoma of Breast are reported worldwide. The incidence of invasive Carcinoma of Breast and mortality in American women in 2017 was 252,710 and 40,610 respectively as quoted by a study. According to latest survey conducted by the Indian Council of Medical Research (ICMR) in India, there were an estimated 150,000 new cases of Carcinoma of Breast in the year 2016. The rise in both Carcinoma of Breast incidence and mortality, therefore, necessitates an examination of risk factors associated with this disease. Molecular subtypes-based classification system characterized by the presence or absence of immunohistochemical expressions like Progesterone receptor (PR), Estrogen receptor (ER), and Human epidermal growth factor receptor 2 (HER2) may show certain limitations. The gene encoding ACE (Angiotensin Converting Enzyme,) in humans is located in the chromosome 17 (17q23), consisting of 26 exons and 25 introns and spanning 21 kb. ACE is a zinc dependent dipeptidyl carboxypeptidase which catalyzes conversion of inactive decapeptide Angiotensin I (Ang I) to active octapeptide Ang II . Ang II mediates physiological effects by binding to two subtypes of the receptors, AGTR1 and Angiotensin II receptor type II (AGTR2), which belongs to superfamily of G-protein-coupled receptors (GPCRs).So, keeping all these physiological effects in mind, this study was conducted to see the role of ACE gene in carcinoma of breast. Methods: From confirm and control cases 3.0 ml of venous blood from each study subject was collected in an EDTA vial. Genomic DNA was extracted by phenol-chloroform method. The genotyping was performed by using PCR (Polymerase Chain reaction), using gene-specific primers. The resulting PCR products were separated on 2% agarose gels using ethidium bromide stain and visualized under UV light. The clinicopathologic parameters of breast cancer patients were obtained from medical records. Results: Of the 10 patients, 3 (30%) had Deletion/deletion genotype DD, 6 (60%) had ID, and 1 (10%) had II genotypes. In control subjects, 2 (20%) had DD, 6 (60%) had ID, and 2 (20%) had II genotypes. Conclusion: The results showed no significant association of ACE gene polymorphism with breast cancer (p>0.05). There is a necessity to conduct large-scale studies with adequate methodological quality and larger sample size in order to come to a definitive conclusion.