• Korean Journal of Clinical Laboratory Science
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• v.55 no.2
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• pp.93-104
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• 2023

This study aimed to identify new markers that cause lung adenocarcinoma by analyzing mutation hotspots for the top five genes with high mutation frequency in lung adenocarcinoma in Koreans by next generation sequencing (NGS) analysis. The association between TP53 mutation types and patterns with smoking, a major cause of lung cancer, was examined. The clinicopathological characteristics of lung adenocarcinoma patients with TP53 P72R SNPs were analyzed. In Korean lung adenocarcinoma cases, regardless of the smoking status, the TP53 P72R SNP was the most frequently occurring mutational hotspot, in which the nucleotide base was transversed from C to G, and the amino acid was substituted from proline to arginine at codon 72 of TP53. An analysis of the clinicopathological characteristics of lung adenocarcinoma cases with TP53 P72R SNP revealed no significant correlation with the patient's age, gender, smoking status, and tumor differentiation, but a significant correlation with low stage (P-value =0.026). This study confirmed an increase in TP53 rather than EGFR, which was reported as the most frequent mutations in lung adenocarcinoma in Koreans through NGS. Among them, TP53 P72R SNP is the most frequent regardless of smoking status.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6505-6510
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• 2014

Objective: This study was conducted to identify whether polymorphic variants of set domain-containing protein 8 (SET8) and tumor protein p53 (TP53) codon 72, either independently or jointly, might be associated with increased risk for cervical cancer. Methods: We genotyped SET8 and TP53 codon 72 polymorphisms of peripheral blood DNA from 114 cervical cancer patients and 200 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. Results: The frequency of SET8 CC (odds ratios (OR) = 2.717, 95% CI=1.436-5.141) or TP53 GG (OR=2.168, 95% CI=1.149-4.089) genotype was associated with an increased risk of cervical cancer on comparison with the SET8 TT or TP53 CC genotypes, respectively. In additional, interaction between the SET8 and TP53 polymorphisms increased the risk of cervical cancer in a synergistic manner, with the OR being 9.913 (95% CI=2.028-48.459) for subjects carrying both SET8 CC and TP53 GG genotypes. Conclusion: These data suggest that there are significant associations between the miR-502-binding site SNP in the 3'-UTR of SET8 and the TP53 codon 72 polymorphism with cervical cancer in Chinese, and there is a gene-gene interaction.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2917-2922
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• 2014

Background: The p53-binding protein 1 (TP53BP1) gene may be involved in the development of cancer through disrupting DNA repair. However, investigation of associations between TP53BP1 rs2602141 A/C polymorphism and cancer have yielded contradictory and inconclusive outcomes. We therefore performed a meta-analysis to evaluate the association between the TP53BP1 rs2602141 A/C polymorphism and cancer susceptibility. Materials and Methods: Published literature from PubMed, Medline, the Cochrane Library, EMbase, Web of Science, Google (scholar), CBMDisc, Chongqing VIP database, and CNKI database were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed or random-effects models. Publication bias was estimated using funnel plots, Begg's and Egger's test. Results: A total of seven studies (3,018 cases and 5,548 controls) were included in the meta-analysis. Our results showed that the genotype distribution of TP53BP1 rs2602141 A/C was not associated with cancer risk overall. However, on subgroup analysis, we found that TP53BP1 rs2602141 A/C was associated with cancer risk within an allele model (A vs C, OR=1.14, 95%CI: 1.01-1.29) and a codominant model (AA vs CC, OR=1.36, 95%CI: 1.06-1.74) in Asians rather than in Caucasians. Subgroup analysis by cancer type, genotype, and with or without adjustment for controls showed no significant association. Conclusions: The findings suggested an association between rs2602141 A/C polymorphism in TP53BP1 gene and increased risk of cancer in Asians.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4305-4309
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• 2012

Background: Previous studies on the association between the TP53 Arg72Pro polymorphism and hepatocellular carcinoma (HCC) risk obtained controversial findings. This study aimed to quantify the strength of the association by meta-analysis. Methods: We searched PubMed and Wangfang databases for published studies on the association between the TP53 Arg72Pro polymorphism and HCC risk, using the pooled odds ratio (OR) with its 95% confidence intervals (95% CI) for assessment. Results: 10 studies with a total of 2,026 cases and 2,733 controls were finally included into this meta-analysis. Overall, the TP53 Arg72Pro polymorphism was not associated with HCC risk (all P values greaterth HCC risk in Caucasians in three genetic models (For Pro versus Arg, OR = 1.20, 95%CI 1.03-1.41; For ProPro versus ArgArg, OR = 1.74, 95%CI 1.23-2.47; For ProPro versus ArgPro/ArgArg, OR = 1.85, 95%CI 1.33-2.57). However, there was no significant association between the TP53 Arg72Pro polymorphism and HCC risk in East Asians (all P values greater than 0.10). No evidence of publication bias was observed. Conclusion: Meta-analyses of available data suggest an obvious association between the TP53 Arg72Pro and HCC risk in Caucasians. However, the TP53 Arg72Pro polymorphism may have a race-specific effect on HCC risk and further studies are needed to elucidate this possible effect.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10893-10898
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• 2015

Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas. We investigated the prognostic significance of $O^6$-methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.347-350
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• 2012

TP53 is the mostly commonly mutated gene in many cancers and the P53 tumor suppressor protein is involved in multiple cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control and apoptosis. A common single nucleotide polymorphism located within the proline rich region of TP53 gene at codon 72 in exon 4 encodes either proline or arginine. TP53 Arg 72 is more active than TP53 Pro 72 in inducing apoptosis. The aim of this study was to understand the association of the 72 codon polymorphism with acute leukemia development and prognosis. A total of 288 acute leukemia cases comprising 147 acute lymphocytic leukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis of the TP53 72 polymorphism using PCR-RFLP method. Significant association of homozygous arginine genotype with AML was observed (${\chi}^2$- 133.53; df-2, p < 0.001. When data were analyzed with respect to clinical variables, elevation in mean WBC, blast %, LDH levels and slight reduction in DFS in ALL cases with the arginine genotype was observed. In contrast, AML patients with Pro/Pro had elevated WBC, Blast%, LDH levels with slightly reduced DFS. Our study indicates that Arg/Arg genotype might confer increased risk to development of acute myeloid leukemia.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1603-1609
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• 2014

Background: The response to treatment and overall survival (OS) of patients with acute myeloid leukemia (AML) is variable, with a median ranging from 6 months to 11.5 years. TP53 is associated with old age, chemotherapy resistance, and worse OS. Using genetic sequencing, we set out to look at our own experience with AML, and hypothesized that both TP53 mutations and SNPs at codon 72 would mimic the literature by occurring in a minority of patients, and conferring a worse OS. Materials and Methods: We performed a pilot study of randomly selected, newly diagnosed AML patients at Mount Sinai Medical Center, diagnosed from 2005-2008 (n=10). TP53 PCR sequencing was performed using DNA from bone marrow smears. Analysis was accomplished using Mutation Surveyor software with confirmation of the variants using the COSMIC and dbSNP databases. Results: Fewer than half of the patients harbored TP53 mutations (40%). There was no significant difference in OS based on gender, AML history, risk-stratified karyotype, or TP53 mutation. There were possible trends toward improved survival among patients less than 60 (11 vs 4 months, p=0.09), Hispanics (8 vs 1 months, p=0.11), and those not harboring SNP P72R (8 vs 2 months, p=0.10). There was a significant improvement in survival among patients with better performance status (28 vs 4 months, p=0.01) and those who did not have a complex karyotype (8 vs 1 months, p=0.03). The most commonly observed TP53 mutation was a missense N310K (40%) and the most commonly observed SNP was P72R (100.0%). Conclusions: Our study confirms previous reports that poor PS and the presence of a complex karyotype are associated with a decreased OS. In our cohort, TP53 mutations were relatively common, occurring more frequently in male patients with an adverse karyotype. Although there was no significant difference in survival between TP53 mutated and un-mutated patients, there was a possible trend toward worse OS among patients with SNP P72R. Larger studies are needed to validate these findings.

• Clinics in Shoulder and Elbow
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• v.25 no.4
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• pp.296-303
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• 2022

Background: A previous study reported that hyperlipidemia increases the incidence of tears in the rotator cuff tendon and affects healing after repair. The aim of our study was to compare the gene and protein expression of torn rotator cuff tendons in patients both with and without hypercholesterolemia. Methods: Thirty patients who provided rotator cuff tendon samples were classified into either a non-hypercholesterolemia group (n=19, serum total cholesterol [TC] <200 mg/dL) and hypercholesterolemia group (n=11, serum TC ≥240 mg/dL) based on their concentrations of serum TC. The expression of various genes of interest, including COL1A1, IGF1, IL-6, MMP2, MMP3, MMP9, MMP13, TNMD, and TP53, was analyzed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). In addition, Western blot analysis was performed on the proteins encoded by interleukin (IL)-6 and TP53 that showed significantly different expression levels in real-time qRT-PCR. Results: Except for IGF1, the gene expression levels of IL-6, MMP2, MMP9, and TP53 were significantly higher in the hypercholesterolemic group than in the non-hypercholesterolemia group. Western blot analysis confirmed significantly higher protein levels of IL-6 and TP53 in the hypercholesterolemic group (p<0.05). Conclusions: We observed an increase in inflammatory cytokine and matrix metalloproteinase (MMP) levels in hypercholesterolemic patients with rotator cuff tears. Increased levels of IL-6 and TP53 were observed at both the mRNA and protein levels. We suggest that the overexpression of IL-6 and TP53 may be a specific feature in rotator cuff disease patients with hypercholesterolemia.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.915-921
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• 2012

Background: Previous studies investigating the association between TP53 Arg72Pro polymorphism and gastric cancer (GC) risk in Asian population have reported controversial results. Thus, a meta-analysis was performed. Methods: A comprehensive literature search was conducted and 17 case-control studies were finally included, involving a total of 5,990 GC cases and 6,812 controls. Subgroup analyses were performed by the sample size. Results: Meta-analysis of all 17 studies showed variant genotypes of TP53 Arg72Pro to be associated with an elevated GC risk in three genetic comparison models ($OR_{Pro\;vs.\;Arg}$=1.13, 95%CI 1.03-1.25, $P_{OR}$=0.01; $OR_{Homozygote\;comparison\;model}$=1.33, 95%CI 1.07-1.64, $P_{OR}$=0.009; $OR_{Dominant\;genetic\;model}$=1.13, 95%CI 1.05-1.22, $P_{OR}$=0.002). Besides, a more obvious association was observed after the heterogeneity was decreased (all P values less than 0.001). This association was further identified by both subgroup and sensitivity analyses. Conclusions: This meta-analysis suggests the Pro variant of TP53 Arg72Pro contributes to gastric cancer risk in Asians.

• BMB Reports
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• v.52 no.6
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• pp.379-384
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• 2019

Epithelial-mesenchymal transition (EMT) is widely-considered to be a modulating factor of anoikis and cancer metastasis. We found that, in MDA-MB-231 cells, TP53I11 (tumor protein P53 inducible protein 11) suppressed EMT and migration in vitro, and inhibited metastasis in vivo. Our findings showed that hypoxic treatment upregulated the expression of $HIF1{\alpha}$, but reduced TP53I11 protein levels and TP53I11 overexpression reduced $HIF1{\alpha}$ expression under normal culture and hypoxicconditions, and in xenografts of MDA-MB-231 cells. Considering $HIF1{\alpha}$ is a master regulator of the hypoxic response and that hypoxia is a crucial trigger of cancer metastasis, our study suggests that TP53I11 may suppress EMT and metastasis by reducing $HIF1{\alpha}$ protein levels in breast cancer cells.