Association of Non-Synonymous Polymorphism in C-Myc Gene with Increased Risk of Breast Cancer

Abstract

C-myc is involved in expression of about 15% of human genes and regulates many physiological functions such as cell cycle, metabolism, survival, cell adhesion, cytoskeleton, miRNA and protein biosynthesis. Additionally, c-myc also plays role in cell senescence, apoptosis and responses related to DNA damage. C-myc protooncogene is strongly regulated by transcription factors. High expressions of c-myc in transformed cancerous cells as compared to normal cells stimulate several signaling pathways which lead to tumor progression. Association of c-myc polymorphisms in breast cancer is still unclear. Generally, non-synonymous single nucleotide polymorphisms (nsSNPs) or missense SNPs are associated with increased risk of disease. These non-synonymous SNPs cause alteration in structure as well as function of the protein. In this study role of non-synonymous single nucleotide polymorphisms rs4645959 Asn11Ser (31A>G) and rs4645960 Gly160Cys (477G>T) with increased risk of breast cancer was determined. Demographic characters were determined from 403 breast cancer patients. Genotype was determined by amplification of SNP rs4645959 by using Amplification Refractory Mutation System (ARMS) on 403 breast cancer subjects and 269 controls. Polymerase chain reaction and Ristriction Fragment Length Polymorphism was carried out for rs4645960 on 348 breast cancer cases and 164 controls. Study on Pakistani population revealed higher risk of breast cancer associated with the mutant Asn11Ser as compared to heterozygous variant (OR=1.89, CI=1.26-2.82 P=0.011). The subject control study on 348 subjects and 164 controls indicated the relevance of heterozygous polymorphism of Gly160Cys with increased risk of breast cancer (OR=2.08, CI=1.22-3.53, P=0.006).