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Objective To explore the association of single nucleotide polymorphism ( SNP ) in TP53 Arg72Pro (rs1042522) locus with thyroid cancer risk in human. Methods Articles involved in the association between SNP in TP53 Arg72Pro ( rs1042522) locus and thyroid cancer risk were retrieved from PubMed, Embase, and Web of Science databases, and studies which met the inclusion criteria were included. The meta-analysis, sensitivity analysis, subgroup analysis, and the assessment of publication-bias were performed by Stata 14. 0 software. The odds ratio ( OR) and their corresponding 95％ Confidence Intervals ( CI) were used to determine the strength of association between SNP in TP53 Arg72Pro locus and thyroid cancer risk. Results Thirteen case-control studies were eligible for this meta-analysis, including 2112 thyroid cancer cases and 4000 control subjects. Overall, mutated homozygous genotype ( Pro/Pro) in TP53 Arg72Pro ( rs1042522) locus was associated with significantly increased thyroid cancer risk(Recessive model, OR=1.78, 95％CI 1.24-2.56, P=0.002), showing a significantly higher Pro mutation frequency among thyroid cancer patients ( Allelic model, OR=1. 35, 95％ CI 1. 12-1. 63, P=0.002). In the stratified analysis, mutated homozygous genotype (Pro/Pro) in TP53 Arg72Pro (rs1042522) locus was only asscociated with significantly increased thyroid cancer risk among Asians, but not among Europeans and South Americans;mutated homozygous genotype ( Pro/Pro) in TP53 Arg72Pro ( rs1042522) locus was asscociated with significantly increased risk of papillary thyroid carcinomas ( PTC) among total population, but not medullary thyroid carcinomas. Conclusion There is a significant association between TP53 Arg72Pro polymorphism in TP53 and thyroid cancer risk, and the mutated homozygous genotype ( Pro/Pro) in this locus of TP53 maybe a risk factor for thyroid carcinoma among Asians.
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IntroductionThe p53 gene is frequently mutated in various forms of human cancers. The p53 signaling pathway isactivated by endogenous and exogenous stress signals and induces growth arrest, cellular senescenceand apoptosis. A common polymorphism occurs at codon 72 of the p53 has been demonstrated that itmight be associated with bladder cancer risk. However, results of researches related to this topic werecontroversial and more investigations and samples size needed.GoalTo evaluate TP53 Arg72Pro polymorphism in Mongolian patients with bladder cancer.Materials and MethodWe evaluated TP53 Arg72Pro polymorphism in DNA samples from 82 patients with bladder cancerand 82 age and gender matched healthy subjects using polymerase chain reaction-based restrictionfragment length polymorphism. All enrolments of this study were Mongolians. The association betweeneach genotype of TP53 Arg72Pro and bladder cancer risk was examined by the odds ratio and 95%confi dence interval, using logistic regression analysis. The early age onset of bladder cancer patientswas also evaluated among different genotypes of TP53 Arg72Pro.ResultsThe proportion of the polymorphism of TP53 Arg72Pro were RR 53.7% (n=44); PR 34.1% (n=28); andPP 12.2% (n=10) in the bladder cancer patients, whereas RR 52.4% (n=43); PR 28% (n=23); and PP19.6% (n=16) in healthy controls. The PR genotype increased the risk of bladder cancer (OR1.189;95% CI 0.42-0.75; p=0.997) in Mongolian people, whereas PP genotype protected from the cancer(OR=0.610; 95% CI 0.22-0.44, p=0.998) compared to the RR, respectively, however signifi cance isweak. Moreover, there was no association between each genotype of TP53 Arg72Pro (RR=52; PR=54;PP=58) and early onset of bladder cancer in the Mongolian population.Conclusion: Our result indicates that the PR genotype tends to increase the risk of bladder canceramong Mongolians. RR genotype of TP53 Arg72Pro is more prevalent among Mongolians.
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Arg72Pro SNP of p53 has been associated with many types of cancer as well as with survival and longevity. We evaluated the Arg72Pro SNP frequencies of a Brazilian birth cohort and their association with current, demographic and birth epidemiological parameters available. In 1982, all hospital births of Pelotas, southern Brazil, were identified and studied prospectively. In 2004–5, blood samples were collected and DNA extracted. PCR-RFLP was used to genotype the Arg72Pro SNP in 3794 individual samples of the Brazil birth cohort and DNA sequencing was performed to confirm the genotypes. The genotype distribution, which was in Hardy–Weinberg equilibrium, showed a predominance of the arginine amino acid with a frequency of 46.9% Arg/Arg, 42.2% Arg/Pro and 10.9% Pro/Pro. The allele frequency was 0.68 of Arginine and 0.32 of Proline. The Arg72Pro SNP genotype and allelic frequency were related to skin colour where proline amino acid was observed more among black subjects, while arginine amino acid was observed more among white subjects. The individuals without family history of cancer and those with low birth weight were associated with arginine amino acid. The Arg72Pro SNP was strongly associated with important epidemiological variables confirming that genetic profiles on cohort studies can improve our understanding of the susceptibility of diseases and its risk factors.
ABSTRACT
The TP53 tumor suppressor gene codifies a protein responsible for preventing cells with genetic damage from growing and dividing by blocking cell growth or apoptosis pathways. A common single nucleotide polymorphism (SNP) in TP53 codon 72 (Arg72Pro) induces a 15-fold decrease of apoptosis-inducing ability and has been associated with susceptibility to human cancers. Recently, another TP53 SNP at codon 47 (Pro47Ser) was reported to have a low apoptosis-inducing ability; however, there are no association studies between this SNP and cancer. Aiming to study the role of TP53 Pro47Ser and Arg72Pro on glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of these SNPs in 94 gliomas (81 astrocytomas, 8 ependymomas and 5 oligodendrogliomas) and in 100 healthy subjects by the polymerase chain reaction-restriction fragment length polymorphism approach. Chi-square and Fisher exact test comparisons for genotype distributions and allele frequencies did not reveal any significant difference between patients and control groups. Overall and disease-free survivals were calculated by the Kaplan-Meier method, and the log-rank test was used for comparisons, but no significant statistical difference was observed between the two groups. Our data suggest that TP53 Pro47Ser and Arg72Pro SNPs are not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.