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

Raju S R Adduri,Sandeep N Madana,Murali Dharan Bashyam,Rajender Katamoni,Ramaswamy Pandilla,Viswakalyan Kotapalli,Arun Kumar Paripati,Xin-Yuan Guan

doi:10.1371/journal.pone.0114002

Raju S R Adduri, Sandeep N Madana + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0114002

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Journal: PloS one	Publication Date: Dec 1, 2014
Citations: 11	License type: CC BY 4.0

Affiliation: Centre for DNA Fingerprinting and Diagnostics

Abstract

PurposeThe 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.MethodsWe 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.ResultsPro72 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.ConclusionsOur 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.

Highlights

Squamous Cell Carcinoma of the Oral Tongue (SCCOT) is a common form of head and neck squamous cell carcinoma (HNSCC) and its incidence is consistently increasing worldwide [1]
We analyzed the distribution of p53 codon 72 genotypes in SCCOT and ESCC with respect to healthy controls (Figure 1) as described in materials and methods section. 26 (23.6%), 53 (48.2%) and 31 (28.2%) control samples harbored Pro/ Pro, Pro/Arg and Arg/Arg genotypes, respectively, exhibiting thereby no significant enrichment of one allele over the other (Table 1)
Several studies conducted on mixture of Head and Neck squamous cell carcinoma (HNSCC) samples did not detect any significant association with TP53 codon 72 polymorphism [31,32,33] perhaps due to heterogeneity of tumor subtypes

Summary

Introduction

Squamous Cell Carcinoma of the Oral Tongue (SCCOT) is a common form of head and neck squamous cell carcinoma (HNSCC) and its incidence is consistently increasing worldwide [1]. SCCOT is known to be aggressive and is associated with higher rates of occult and nodal metastasis when compared to other HNSCC subtypes [4]. It is often associated with poor survival which has not improved significantly over the past four decades [5, 6]. A similar trend in increase of GERD has been noted in Asian countries in the last few decades, ESCC remains the predominant EC subtype [10], suggesting possibility of role of genetic factors. Due to its closer location to neck and similarities in tumorigenesis pathways, ESCC is sometimes classified with HNSCC

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