‘BRCA1’ RESPONSIVENESS TOWARDS BREAST CANCER-A POPULATION-WISE PHARMACOGENOMIC ANALYSIS Original Article PREETHI M. IYER 1,2 , SANJAY KUMAR P. 2 , KARTHIKEYAN S. 2 , P. K. KRISHNAN NAMBOORI 2* 1 Dept of Electronics and Communications Engineering, Amrita School of Engineering, Coimbatore, Amrita Vishwa Vidyapeetham, Amrita University, India, 2 Received: 13 Jun 2016 Revised and Accepted: 22 Jul 2016 Computational Chemistry Group (CCG), Amrita School of Engineering, Coimbatore, Amrita Vishwa Vidyapeetham, Amrita University, India Email: n_krishnan@cb.amrita.edu ABSTRACT Objective: In the present pharmacogenomic work, the genetic, epigenetic and environmental factors associated with BRCA1 induced breast cancer, cancer proneness and its variants across different populations like Indian, Netherland, Belgium, Denmark, Austrian, New Zealand, Sweden, Malaysian and Norwegian and the ‘mutation and methylation-prone’ region of BRCA1 have been computed. Methods: The global variations associated with the disease have been identified from the ‘Leiden open variation database (LOVD 3.0)’ and ‘Indian genome variation database (IGVDB)’. The variants, ‘single nucleotide polymorphisms (SNPs)’ are then characterized. The epigenetic factors associated with breast cancer have been identified from the clinical reports and further scrutinized using EpiGRAPH tool. The various contributing environmental factors responsible for the variations have been considered. Results: All the variants across different populations such as Indian, Netherland, Belgium, Denmark, Austrian, New Zealand, Sweden, Malaysian and Norwegian are found to be in a specific transcript of BRCA1 that ranges within 41,196,312-41,277,500 (81,189 base pairs) of the chromosome 17. Two ‘single nucleotide variations (SNVs)’ (5266dupC: rs397507246 and 68_69delAG: rs386833395) have been identified as risk factors in hereditary breast and ovarian cancer syndrome in the global population and 39 SNPs have been identified as pathogenic and deleterious. ‘Evolutionary history’ seems to be the most significant attribute in the predictability of methylation of BRCA1. Unhealthy dietary habits, obesity, use of unsafe cosmetics, estrogen exposure, ‘hormone replacement therapy (HRT)’, use of oral contraceptives and smoking are the major environmental risk factors associated with breast cancer incidence. Conclusion: This chromosome location (41,196,312-41,277,500 (81,189 base pairs)) can be considered as the population-specific sensitive region corresponding to BRCA1 mutation. This supports the fact that stabilization within the region can be a promising technique to control the epigenetic variants associated with the global position. The global variation in the proneness of the disease may be due to a cumulative effect of genetic, epigenetic and environmental factors subject to further experimentations with identical variations and populations. Keywords: BRCA1, Epigenetic factors, Environmental factors, Mutation, Breast cancer, Population analysis © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ijpps.2016.v8i9.13457 INTRODUCTION Cancer is one of the leading causes of death worldwide, and the incidence rate is increasing day by day according to information gathered from the ‘National Health Portal of India.' The most familiar cancer type seen among women in the world is breast cancer [1]. The distribution of annual death rate due to breast cancer across various countries is included in fig. 1 and is worth focusing. Fig. 1: Annual death rate of breast cancer across different countries [2] Along with the global population, the Indian population is also prone but comparatively less to breast cancer with an annual death rate of 13.65% [2]. On the basis of a survey performed by ‘Indian Council of Medical Research (ICMR)’, it has been found that the occurrence of breast cancer in India has doubled during the period of 1982-2005. BRCA1 is the prominent mutation leading to breast cancer [3]. In normal cells, this gene is involved in DNA repair, transcription regulation, and tumor suppression. The BRCA1 can be spotted at the 21 st It is prevailing that breast cancer is caused by a blend of genetic, epigenetic and environmental factors [7, 8]. The epigenetic regulation normally comprises of the components, DNA methylation, histone modifications and the existence of miRNA. These mechanisms seem to play a major role in altering the gene expression levels within a living cell. Epigenetic factors can be modified by external as well as internal environmental factors such as obesity, excess dietary fats, heavy metals, estrogen content, alcohol, etc. [8, 9]. position of chromosome 17 at the q arm. Mutations in BRCA1 gene are involved in the formation of abnormal BRCA1 proteins that result in fallopian tube cancer, ovarian cancer, breast cancer, prostate cancer, pancreatic cancer, etc. The ‘single nucleotide polymorphism (SNP)’ has been considered as the major DNA marker, corresponding to the genetic signature of the disease [4-6]. Hence, identification and characterization of SNP corresponding to proneness of breast cancer are helpful in making a global analysis of the situation. In the present manuscript, the genetic, epigenetic and environmental factors associated with BRCA1 induced breast cancer, cancer proneness and its variants across different populations like Indian, Netherland’s, Belgium, Denmark, Austrian, New Zealand, Sweden, Malaysian and Norwegian has been provided. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 9, 2016