A Computational Analysis of Polymorphisms in Tumor Suppressor Genes Present in Colorectal Cancer Pathway

Single nucleotide polymorphisms are the most common form of genetic variations between human genome they play significant role to understand the genetic basis of various complex human diseases. There is a major challenge to categorize the functional SNPs in a particular disease. The computational methods namely SIFT, PolyPhen, FastSNP, I-Mutant 2.0 were used to predict the various function of single nucleotide polymorphisms (SNPs). These are extensively used to understand the biological basis of diverse human diseases. In this work eight tumor suppressor genes (TSG) viz. SMAD2, SMAD3, SMAD4, BAX, DCC, APC, P53 and TGFBR2 present in the colorectal cancer pathway mentioned in KEGG database were analyzed. A total of 22613 SNP were present in the TSG of colorectal pathway in dbSNP. Twenty three nsSNP were found to be deleterious by SIFT. The finding of server PolyPhen showed thirty five nsSNP to be damaging. The fifteen nsSNP (rs76321625, rs2229333, rs17849781, rs55832599, rs28934572, rs112833742, rs74755144, rs76772194, rs1054708, rs111298989, rs1801724 rs61762550, rs114457508, rs55751315, rs111319732,) predicted to be highly deleterious by SIFT and PolyPhen respectively. A noteworthy nsSNP (rs55832599) found to be highly deleterious with a SIFT score 0.00 and PSIC score difference of 3.065 predicted to have a damaging effect. Two nsSNPs were present in the splicing site using FASTSNP. In all the analyzed TSG genes, we have found 15 nsSNPs with increase stability and 79 nsSNPs showed decrease in the stability. The analysis predicted from the result provides useful information about SNPs that affect the polymorphism on phenotype in tumor suppressor genes which contribute the susceptibility of colorectal cancer.