TP53 Pro72 allele is enriched in oral tongue cancer and frequently mutated in esophageal cancer in India

Abstract

Purpose: The tumor suppressor p53 is known to be inactivated frequently in various cancers. In addition, germline polymorphisms in TP53 are known to affect protein function and influence risk of developing different types of cancers. In this study, we analyzed the association of TP53 Pro72Arg polymorphism with squamous cell carcinoma of oral tongue (SCCOT) and esophagus (ESCC) in India.

Methods: We assessed the distribution of TP53 Pro72Arg polymorphism in one hundred and fifteen and eighty two SCCOT and ESCC patients, respectively, with respect to one hundred and ten healthy controls from the same population. In addition, we analyzed association of the polymorphism with several clinico-pathological and molecular parameters.

Results: Pro72 allele was significantly enriched in SCCOT patients compared to the healthy control group but neither allele was enriched in ESCC. Interestingly, Pro72 allele was preferentially mutated in ESCC which was confirmed by analysis of samples heterozygous for Pro72Arg.

Conclusions: Our study revealed the association of Pro72 allele with SCCOT suggesting the effect of this polymorphism on SCCOT risk. Preferential mutation of Pro72 allele exclusively in ESCC indicates the need for further studies to understand the tissue specific effect of p53 polymorphism.

Figure 1. Identification of the three different p53 codon 72 genotypes.

Panel A, PCR-RFLP analysis confirmed by allele specific PCR performed as described in the materials and methods section. M, 50 bp DNA ladder; 1, Pro/Pro; 2, Pro/Arg; 3, Arg/Arg; and C, No template control. Panel B, Sanger sequencing. Pro/Pro (left), Pro/Arg (middle) and Arg/Arg (right).

Figure 2. TP53 mutation identified in Pro72 or Arg72 allele in fourteen ESCC samples heterozygous for p53 codon 72 polymorphism.

Electrophoretograms showing mutation (left) and codon 72 polymorphism (right) for each of the fourteen samples are shown. Location of missense and deletion mutations are indicated by arrows and bars, respectively. Proline (CCC) or Arginine (CGC) codons are indicated by a bar.