• Preethi M. Iyer Dept of Electronics and Communications Engineering, Amrita School of Engineering, Coimbatore, Amrita Vishwa Vidyapeetham, Amrita University, India
  • Sanjay Kumar P. Computational Chemistry Group (CCG), Amrita School of Engineering, Coimbatore, Amrita Vishwa Vidyapeetham, Amrita University, India
  • Karthikeyan S. Computational Chemistry Group (CCG), Amrita School of Engineering, Coimbatore, Amrita Vishwa Vidyapeetham, Amrita University, India
  • P. K Krishnan Namboori Computational Chemistry Group (CCG), Amrita School of Engineering, Coimbatore, Amrita Vishwa Vidyapeetham, Amrita University, India


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


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1. Ali I, Wani WA, Saleem K. Cancer scenario in India with future perspectives. Cancer Ther 2011;8:56-70.
2. All cancers death rate by country. World Life Expectancy; 2014. Available from: http://www.worldlifeexpectancy.com/cause-of-death/all-cancers/by-country/. [Last accessed on 02 Jun 2016].
3. Kesavan S, Kodous A, Rajkumar T. Computational analysis of mutations in really interesting new gene finger domain and BRCA1 C terminus domain of breast cancer susceptibility gene. Asian J Pharm Clin Res 2016;9:96–102.
4. Namboori PKK, Vineeth KV, Rohith V, Hassan I, Sekhar L, Sekhar A, et al. The ApoE gene of alzheimer’s disease (AD). Funct Integr Genomics 2011;11:519–22.
5. Jehan T, Lakhanpaul S. Single nucleotide polymorphism (SNP)–Methods and applications in plant genetics: a review. Indian J Biotechnol 2006;5:435–59.
6. Bhardwaj S, Balgir PP, Goel RK. Pharmacogenomics and personalized management of hypertension. J Crit Rev 2015;2:1–6.
7. Breast Cancer Risk and Environmental Factors. National Institute of Environmental Health Sciences; 2012. Available from: https://www.niehs.nih.gov/health/assets/docs_a_e/environmental_factors_and_breast_cancer_risk_508. pdf. [Last accessed on 02 Jun 2016].
8. Aguilera O, Fernandez AF, Munoz A, Fraga MF. Epigenetics and environment: a complex relationship. J Appl Physiol 2010;109:243–51.
9. Hilakivi L, Clarke. Estrogens, BRCA1, and breast cancer. Cancer Res 2001;60:4993–5001.
10. HGMD®. The Human Gene Mutation Database; 2015. Available from: http://www.hgmd.cf.ac.uk/ac/index.php. [Last accessed on 06 Jan 2016].
11. Fokkema IFAC, Taschner PEM, Schaafsma GCP, Celli J, Laros JFJ, den Dunnen JT. LOVD v.2.0: the next generation in gene variant databases. Hum Mutat 2011;32:557–63.
12. Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 2001;29:308–11.
13. Ng PC, Henikoff S. Predicting deleterious amino acid substitutions. Genome Res 2001;11:863–74.
14. Yates A, Akanni W, Amode MR, Barrell D, Billis K, Carvalho-Silva D, et al. Ensembl 2016. Nucleic Acids Res 2016;44:D710-6.
15. Kuo HC, Lin PY, Chung TC, Chao CM, Lai LC, Tsai MH, et al. DBCAT: database of CpG islands and analytical tools for identifying comprehensive methylation profiles in cancer cells. J Comput Biol 2011;18:1013–7.
16. Bock C, Halachev K, Büch J, Lengauer T. EpiGRAPH: user-friendly software for statistical analysis and prediction of (epi) genomic data. Genome Biol 2009;10:R14.
17. The Indian Genome Variation Consortium. The Indian Genome Variation database (IGVdb): a project overview. Hum Genet 2005;118:1–11.
18. Herceg Z. Epigenetics and cancer: towards an evaluation of the impact of environmental and dietary factors. Mutagenesis 2007;22:91–103.
19. Hou L, Zhang X, Wang D, Baccarelli A. Environmental chemical exposures and human epigenetics. Int J Epidemiol 2012;41:79–105.
20. Vo AT, Millis RM. Epigenetics and breast cancers. Obstet Gynecol Int 2012:1–10. Doi:10.1155/2012/602720.
21. Falck F, Ricci A, Wolff MS, Godbold J, Deckers P. Pesticides and polychlorinated biphenyl residues in human breast lipids and their relation to breast cancer. Arch Environ Health 1992;47:143–6.
22. Tappel A. Heme of consumed red meat can act as a catalyst of oxidative damage and could initiate colon, breast and prostate cancers, heart disease and other diseases. Med Hypotheses 2007;68:562–4.
23. Stefani ED, Ronco A, Mendilaharsu M, Guidobono M, Deneo-Pellegrini H. Meat intake, heterocyclic amines, and risk of breast cancer: a case-control study in Uruguay. Cancer Epidemiol Biomarkers Prev 1997;6:573–81.
24. Rivas A, Lacroix M, Olea-Serrano F, Laíos I, Leclercq G, Olea N. Estrogenic effect of a series of bisphenol analogues on gene and protein expression in MCF-7 breast cancer cells. J Steroid Biochem Mol Biol 2002;82:45–3.
25. Kumar P, Sharma G, Sharma P, Kumar R. Study on serum lactate dehydrogenase level in precancerous, cancerous, and healthy subjects. Asian J Pharm Clin Res 2016;9:328–30.
26. Lorincz AM. Molecular links between obesity and breast cancer. Endocr Relat Cancer 2006;13:279–92.
27. Lanou AJ. Reduced cancer risk in vegetarians: an analysis of recent reports. Cancer Manag Res 2010;3:1-8.
28. Marsden J. Hormone replacement therapy and breast cancer. Lancet Oncol 2002;3:303–11.
29. Schlesselman JJ. Oral contraceptives and breast cancer. Am J Obstet Gynecol 1990;163:1379–87.
30. Olson AC, Link JS, Waisman JR, Kupiec TC. Breast cancer patients unknowingly dosing themselves with estrogen by using topical moisturizers. J Clin Oncol 2009;27:e103–4.
31. Byford J, Shaw L, Drew MG, Pope G, Sauer M, Darbre P. Oestrogenic activity of parabens in MCF7 human breast cancer cells. J Steroid Biochem Mol Biol 2002;80:49–60.
32. Darbre PD. Environmental oestrogens, cosmetics and breast cancer. Best Pract Res Clin Endocrinol Metab 2006;20:121–43.
33. Terry PD, Rohan TE. Cigarette smoking and the risk of breast cancer in women a review of the literature. Cancer Epidemiol Biomarkers Prev 2002;11:953–71.
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How to Cite
Iyer, P. M., S. K. P., K. S., and P. K. K. Namboori. “‘BRCA1’ RESPONSIVENESS TOWARDS BREAST CANCER-A POPULATION-WISE PHARMACOGENOMIC ANALYSIS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 9, Sept. 2016, pp. 267-70, doi:10.22159/ijpps.2016.v8i9.13457.
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