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Association of TP53 Codon 72 Arg>Pro Polymorphism with Breast and Lung Cancer Risk in the South Asian Population: A Meta-Analysis.

ABSTRACT: BACKGROUND:A transversion missense polymorphism of the TP53 tumor suppressor gene at the codon 72 codes proline instead of arginine causes an altered p53 protein expression and has been found to be associated with an elevated risk of various cancer; especially breast and lung cancer. As the previous case-control studies on the South Asian population have shown controversial results, we performed a meta-analysis to evaluate a precise estimation of the relationship between the TP53 Arg72Pro polymorphism with breast and lung cancer. METHODS:A total of 12 related studies on the South Asian population have been included through comprehensive database searching. Six studies were selected for breast cancer meta-analysis involving 950 cases and 882 controls; the other six studies were for lung cancer meta-analysis including 975 cases and 1397 controls. The results have been determined by using the Review Manager (RevMan) 5.3. Additionally, the stability of our analysis was assessed by heterogeneity, publication bias analysis and sensitivity testing. RESULTS:A significantly increased risk of breast cancer was found in Pro allele (Pro vs. Arg), co-dominant model 2 (Pro/Pro vs. Arg/Arg), dominant model (Pro/Pro + Arg/Pro vs. Arg/Arg). In case of lung cancer, significantly increased risk was found in the allele, co-dominant 1, co-dominant 2, co-dominant 3, dominant, and recessive models. No association with other genetic models with breast and lung cancer risk was found in the South Asian population. CONCLUSIONS:Our results indicate that TP53 Arg72Pro polymorphism is a risk factor for the development of breast cancer and lung cancer in the South Asian population.

SUBMITTER: Jafrin S

PROVIDER: S-EPMC7568897 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Association of TP53 Codon 72 Arg>Pro Polymorphism with Breast and Lung Cancer Risk in the South Asian Population: A Meta-Analysis.

Jafrin Sarah S Aziz Md Abdul MA Anonna Shamima Nasrin SN Akter Tahmina T Naznin Nura Ershad NE Reza Sharif S Islam Mohammad Safiqul MS

Asian Pacific journal of cancer prevention : APJCP 20200601 6

<h4>Background</h4>A transversion missense polymorphism of the TP53 tumor suppressor gene at the codon 72 codes proline instead of arginine causes an altered p53 protein expression and has been found to be associated with an elevated risk of various cancer; especially breast and lung cancer. As the previous case-control studies on the South Asian population have shown controversial results, we performed a meta-analysis to evaluate a precise estimation of the relationship between the TP53 Arg72Pr ...[more]

PMID: 32592343

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Project description:IntroductionThe absence of mutation or promoter hypermethylation in the BRCA2 gene in the majority of breast cancer cases has indicated alternative ways of its involvement, deregulated expression being one possibility. We show how a polymorphism in the 5' untranslated region (UTR) of BRCA2 can serve as one such factor. Based on the hypothesis that variants of genes involved in the same pathway can influence the risk provided for breast cancer, the status of p53 codon 72 polymorphism was also investigated and a possible interaction between the polymorphisms was examined.MethodsThe luciferase reporter assay followed by RNA secondary structure analysis was used for the functional characterization of -26 5' UTR G>A polymorphism in BRCA2. The genotype and the allele frequency for the polymorphisms were determined and relative risk adjusted for age was calculated in a case-control study of 576 individuals (243 patients and 333 controls) from north India.Results-26 G>A polymorphism in the 5' UTR of BRCA2 was found to be functional whereby the A allele increased the reporter gene expression by twice that of the G allele in MCF-7 (P = 0.003) and HeLa (P = 0.013) cells. RNA secondary structure analysis by two different programs predicted the A allele to alter the stability of a loop in the vicinity of the translation start site. Its direct implication in breast cancer became evident by a case-control study in which the heterozygous genotype was found to be protective in nature (P heterozygote advantage model = 0.0005, odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.4 to 0.8), which was further supported by trends observed in a genomic instability study. The p53 codon 72 Arg homozygous genotype was found to be over-represented in patients (P = 0.0005, OR = 2.3, 95% CI = 1.4 to 3.6). The interaction study indicated an increased protection under simultaneous presence of protector genotypes of both the polymorphic loci (P = 0.0001, OR = 0.2, 95% CI = 0.1 to 0.4).ConclusionOur study shows that -26 5' UTR polymorphism in BRCA2 can modulate the fine-tuned regulation of the multifunctional gene BRCA2 and renders risk or protection according to the genotype status in the sporadic form of breast cancer, which is further influenced by the germline genetic backgrounds of codon 72 polymorphism of p53.

Dataset Information

Association of TP53 Codon 72 Arg>Pro Polymorphism with Breast and Lung Cancer Risk in the South Asian Population: A Meta-Analysis.

Publications

Association of TP53 Codon 72 Arg>Pro Polymorphism with Breast and Lung Cancer Risk in the South Asian Population: A Meta-Analysis.

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