Association of p53 codon72 Arg>Pro polymorphism with susceptibility to nasopharyngeal carcinoma: evidence from a case–control study and meta-analysis

Abstract

Tumor suppressor p53 is a critical player in the fight against cancer as it controls the cell cycle check point, apoptotic pathways and genomic stability. It is known to be the most frequently mutated gene in a wide variety of human cancers. Single-nucleotide polymorphism of p53 at codon72 leading to substitution of proline (Pro) in place of arginine (Arg) has been identified as a risk factor for development of many cancers, including nasopharyngeal carcinoma (NPC). However, the association of this polymorphism with NPC across the published literature has shown conflicting results. We aimed to conduct a case–control study for a possible relation of p53 codon72 Arg>Pro polymorphism with NPC risk in underdeveloped states of India, combine the result with previously available records from different databases and perform a meta-analysis to draw a more definitive conclusion. A total of 70 NPC patients and 70 healthy controls were enrolled from different hospitals of north-eastern India. The p53 codon72 Arg>Pro polymorphism was typed by polymerase chain reaction, which showed an association with NPC risk. In the meta-analysis consisting of 1842 cases and 2330 controls, it was found that individuals carrying the Pro allele and the ProPro genotype were at a significantly higher risk for NPC as compared with those with the Arg allele and the ArgArg genotype, respectively. Individuals with a ProPro genotype and a combined Pro genotype (ProPro+ArgPro) also showed a significantly higher risk for NPC over a wild homozygote ArgArg genotype. Additionally, the strength of each study was tested by power analysis and genotype distribution by Hardy–Weinberg equilibrium. The outcome of the study indicated that both allele frequency and genotype distribution of p53 codon72 Arg>Pro polymorphism were significantly associated with NPC risk. Stratified analyses based on ethnicity and source of samples supported the above result.

Carcinogen Metabolism Pathway and Tumor Suppressor Gene Polymorphisms and Gallbladder Cancer Risk in North Indians: A Hospital-Based Case-Control Study

“…Thus, this is the first report regarding the role of the TP53 genetic variant in gallbladder cancer risk in Indians. In contrast, Sahu (2016) reported that both allele frequency and genotype distribution of the TP53 polymorphism are associated with an increased risk of nasopharyngeal carcinoma in a meta-analysis. Our findings that the CC genotype is associated with an increased risk of gallbladder cancer should be examined in additional studies with a larger sample size, a meta-analysis, or a systematic review.…”

Higher incidence of nasopharyngeal carcinoma in some regions in the world confers for interplay between genetic factors and external stimuli

“…Therefore, this high incidence of NPC in specific ethnic groups indicates genetic factors controlling the disease. A number of reports have suggested the role of various genetic factors in association with NPC; particularly, polymorphisms in the histocompatibility locus antigens (HLA), cytochrome P450 2E1 (CYP2 E1), alteration of p53 codon 72 Arg>Pro, and some signaling pathways (82)(83)(84)(85)(86)(87)(88)(89)(90)(91). It has been reported that human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene and human MutY glycosylase homologue (hMUTYH) gene polymorphism is associated to the risk of NPC mainly among women in Chinese population (92).…”

“…Substitution of proline (Pro) in place of arginine (Arg) at codon 72 of the p53 product plays a role in disease susceptibility. Individuals with Arg/Arg genotype have a lower risk of getting NPC compared to the individuals with Arg/ Pro genotype; and those with Pro/Pro genotype have a much higher risk of acquiring NPC (90). Recently, codon 72 Arg>Pro polymorphism and the risk of NPC has been reported in Northestern India.…”

“…On the other hand, EBNA3C can bind directly to p53 and inhibit its DNA binding property; thereby prevents apoptosis by p53 pathway. But the interrelation between EBV infection and the susceptibility of the alteration of p53 codon72 Arg form or codon72 Pro form needs to be investigated thoroughly (90) …”

Histocompatibility locus antigens regions contribute to the ethnicity bias of Epstein‐Barr virus‐associated nasopharyngeal carcinoma in higher‐incidence populations

“…14 Finally, various host genetic factors have been reported to be associated with NPC, particularly polymorphisms in the class I histocompatibility locus antigens (HLA class I), cytochrome P450 2E1 (CYP2 E1), alteration of p53 codon 72 Arg>Pro and some signalling pathways. [15][16][17][18][19][20][21] After initial infection with EBV, antigenic presentations of EBV-derived peptides are involved in the pathogenesis of the virus, eventually leading to cancers like NPC. HLA genes express various proteins of the immune system and help it to process and present foreign antigens, thereby making those antigens vulnerable to immune lysis.…”