title: TP53 alterations and colorectal cancer predisposition in south Indian population: a case-control study.
abstract: The objective of the present study was to investigate the association between TP53 gene single nucleotide polymorphisms (SNPs) and colorectal cancer (CRC) predisposition in south Indian population and to evaluate the role of TP53 expression in the pathophysiology of CRC. A genetic association study was conducted in 103 CRC cases and 107 controls of south Indian origin. We genotyped ten selected TP53 SNPs by polymerase chain reaction-sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pairwise linkage disequilibrium (LD) were assessed by Haploview Software. In addition, to better understand the role of TP53 in the pathophysiology of CRC, the expression pattern was evaluated in analogous tumor and normal tissues from 23 CRC patients by Western blot analysis. The frequencies of Pro72Pro (P = 0.0033) genotype and Ser47/Pro72 (P = 0.00171) haplotype were significantly higher in patients as compared to controls. Strong LD was observed between codon 47 and 72 in cases (D' = 0.32) as compared to controls (D' = 0.21). The polymorphism was not observe at the remaining eight SNPs loci analyzed. Furthermore, increased TP53 expression was observed in tumor tissue than in analogous normal tissue of CRC patients. Interestingly, advanced stage tumors showed more elevated TP53 expression compared to early stage tumors. In conclusion, the TP53 Pro72Pro genotype and Ser47/Pro72 haplotype has an increased risk for CRC predisposition in south Indian population. In addition, elevated TP53 expression appears to be useful prognostic marker for CRC.
authors.affiliation: Department of Zoology, Acharya Nagarjuna University, Guntur, India.
authors.forename: Gopi Krishna
authors.initials: GK
authors.lastname: Singamsetty
authors.forename: Sravanthi
authors.initials: S
authors.lastname: Malempati
authors.forename: Srichandana
authors.initials: S
authors.lastname: Bhogadhi
authors.forename: Ravinder
authors.initials: R
authors.lastname: Kondreddy
authors.forename: Suresh
authors.initials: S
authors.lastname: Govatati
authors.forename: Naveen Kumar
authors.initials: NK
authors.lastname: Tangudu
authors.forename: Sowdamani
authors.initials: S
authors.lastname: Govatati
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: kuraganti
authors.forename: Manjula
authors.initials: M
authors.lastname: Bhanoori
authors.forename: Kondaiah
authors.initials: K
authors.lastname: Kassetty
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53