Population Wise Variation of Breast and Ovarian Cancer-A Pharmacogenomic Approach

Abstract

The somatic mutations in TP53 may be considered as one of the major genomic reasons behind breast and ovarian cancers. These two types of cancers have been reported as the major terminal diseases among women, with breast cancer as the second and ovarian cancer as the fifth cause of death as per the WHO reports last year. However, the proneness of the disease varies from trait to trait and even from person to person. A population-wise analysis of the risk factors associated with the variations results in the study of pharmacogenomic components such as epigenetics, metagenomics, environmental genomics and genomics. The single nucleotide polymorphism (SNP) has been identified as the effective genetic signature to include these variations. For TP53, 27 non-synonymous, pathogenic and deleterious SNPs have been identified in the world populations. Among Indian populations, the SNPs identified are rs1642785, rs1042522, rs8064946, rs12951053, rs1641549, rs1625895 and rs2078486. The frequency of TP53 is found to be high in New Zealand and Australian populations. The methylation probability of TP53 has been predicted through linear SVM using 10 classes of attributes keeping a total of 847 features. The prominent features identified during the epigenetic analysis useful for predicting the possibility of methylation of the gene are the constituents in the DNA sequence, epigenome/chromatin structure and presence of regulatory regions.