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.

Analysis of TP53 Polymorphisms in North Indian Sporadic Esophageal Cancer Patients

“…This result is in agreement with the some earlier reported studies where no association of p.P47S polymorphism was observed in breast cancer (Alawadi et al, 2011;Al-Qasem et al, 2012), bladder cancer (Santos et al, 2011), gliomas , urinary bladder cancer (Jaiswal et al, 2011), colorectal cancer (Sameer et al, 2010) and primary open angle glaucoma patients (Daugherty et al, 2009). On the contrary, significant association of S47 has been reported in Caucasian lung cancer (Felley-Bosco et al, 1993), Brazilian brain tumor (Almeida et al, 2009) and South Indian colorectal cancer (Singamsetty et al, 2014) patients. It has been reported that the S47 phenotype has a decreased capacity to induce apoptosis, to transactivate two p53 target genes (p53AIP1 and PUMA), and to bind to MAPK1 protein as compared with the wild-type P47 phenotype (Li et al, 2005;Murphy, 2006).…”

“…The p.P47S polymorphism has been investigated in various cancers including breast (Alawadi et al, 2011), colorectal (Sameer et al, 2010), gliomas , bladder (Santos et al, 2011), brain (Almeida et al, 2009) and urinary bladder (Jaiswal et al, 2011) cancer. Significant association of S47 has been reported in Caucasian lung cancer (Felley-Bosco et al, 1993) and South Indian colorectal cancer (Singamsetty et al, 2014) patients. So far there is no published report on p.P47S polymorphism in EC.…”

Five P53 SNPs Involved in Low Rectal Cancer Risk and Prognosis in a Chinese Population

“…It was revealed that haplotype A2CCG was associated with a higher CRC risk as compared with the most common haplotype A1GCG, while the four other haplotypes A1CCG, A2GCG, A1GTG and A1GCA were associated with a lower risk28. Another study showed an increased CRC risk for the Pro72/Ser47 haplotype of p53 in south Indian population32. Recently, Kamiza et al found that the CT haplotype (rs1042522/rs12947788) of p53 was related with a reduced CRC risk as compared to the common GC haplotype20.…”

“…A major strength of our study is that all cases collected in the current study were restricted to tumors growing within 8 cm of the anal verge which was classified as low rectal cancer, while most previous studies addressed total colorectal cancer29-32. Limited but significant evidences have revealed the influence of tumor sites on the frequency, type and prognostic and predictive role of p53 mutation in CRC10, 33, 34.…”

TP53 Polymorphisms in Sporadic North Indian Breast Cancer Patients

“…This observation was in contrast to the previous report, showing a significant association between the mutant S47 phenotype and cancer risk (Felley-Bosco et al, 1993). S47 allele was also found to be associated with increased risk of developing colorectal cancer in South Indian population (Singamsetty et al, 2014). It has been reported that the S47 phenotype has a decreased capacity to induce apoptosis, to transactivate two (p53AIP1 and PUMA) p53 target genes, and to bind to MAPK1 protein as compared with the wild-type P47 phenotype (Li et al, 2005;Murphy, 2006).…”