TP53 Pro72 Allele Is Enriched in Oral Tongue Cancer and Frequently Mutated in Esophageal Cancer in India

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.

Gender specific association of TP53 polymorphisms (EX4 215G>C Arg72Pro, IVS3+40‐41ins16, and IVS6+62G>A), with risk of oral cancer subtypes and overall survival of the patients

“…females. This finding is in partial agreement with a small study that had nearly twice the number of males (males ¼ 76, females ¼ 39) as compared to females [25], but differed from a report that found "GC" variant to be protective against oral cancer [26] and from other studies that found no link between the polymorphism and HNSCC [27,28]. The polymorphism was linked to elevated cervical cancer risk in Chinese women, irrespective of HPV status [29].…”

Meta-Analysis Results on the Association Between TP53 Codon 72 Polymorphism With the Susceptibility to Oral Cancer

“…Among the remaining articles, four articles (Tandle et al, 2001 ; Jing et al, 2012 ; Saleem et al, 2013 ; Nagam et al, 2017 ) were not in agreement with HWE ( P < 0.001) and three duplicated data publications were further excluded (Ji et al, 2008 ; Misra et al, 2009 ; Wang et al, 2012 ). We included 21 case-control study involving 3,525 oral carcinoma patients and 3,712 controls (Summersgill et al, 2000 ; Drummond et al, 2002 ; Nagpal et al, 2002 ; Shen et al, 2002 ; Katiyar et al, 2003 ; Kietthubthew et al, 2003 ; Hsieh et al, 2005 ; Mitra et al, 2005 ; Bau et al, 2007 ; Kuroda et al, 2007 ; Chen et al, 2008 ; Lin et al, 2008 ; Tu et al, 2008 ; Kitkumthorn et al, 2010 ; Ihsan et al, 2011 ; Saini et al, 2011 ; Patel et al, 2013 ; Adduri et al, 2014 ; Sina et al, 2014 ; Rao et al, 2017 ; Zarate et al, 2017 ). The characteristics of the selected studies are shown in Table 1 .…”

SMARCD1 is a transcriptional target of specific non‐hotspot mutant p53 forms

“…Informed consent was obtained from patients. Clinicopathological and molecular details of samples (Table S1a) including the status of p53, EGFR, microsatellite instability, human papillomavirus (HPV) infection, and loss of heterozygosity at different tumor suppressor loci were determined in our previous studies (Adduri & Katamoni et al, ; Adduri & Kotapalli et al, ); additional samples were collected and processed as before. p53 immunohistochemistry (IHC) was performed as previously described (Adduri & Kotapalli et al, ).…”

“…Clinicopathological and molecular details of samples (Table S1a) including the status of p53, EGFR, microsatellite instability, human papillomavirus (HPV) infection, and loss of heterozygosity at different tumor suppressor loci were determined in our previous studies (Adduri & Katamoni et al, 2014;; additional samples were collected and processed as before.…”