• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4909-4914
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• 2012

Objective: The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive a more precise estimation of the association between p53 codon 72 polymorphism (Arg72Pro, rs1042522 G>C) and cervical cancer risk among Asians. Methods: A literature search of Pubmed, Embase, Web of Science and CBM databases from inception through June 2012 was conducted. The meta-analysis was performed using STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of any association. Twenty-eight case-control studies were included with a total of 3,580 cervical cancer cases and 3,827 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results showed that the Pro/Pro genotype was associated with increased risk of cervical cancer under the heterozygous model (Pro/Pro vs. Arg/Pro: OR = 1.25, 95%CI: 1.02-1.53, P= 0.005). However, no statistically significant associations were found under four other genetic models (Pro vs. Arg: OR = 0.97, 95%CI: 0.85-1.10, P= 0.624; Pro/Pro + Arg/Pro vs. Arg/Arg: OR = 0.84, 95%CI: 0.70-1.01, P= 0.058; Pro/Pro vs. Arg/Arg + Arg/Pro: OR = 1.13, 95%CI: 0.92-1.39, P= 0.242; Pro/Pro vs. Arg/Arg: OR = 0.97, 95%CI: 0.76-1.22, P= 0.765; respectively). In the subgroup analysis based on country, the Pro/Pro genotype and Pro carrier showed significant associations with increased risk of cervical cancer among Indian populations, but not among Chinese, Japanese and Korean populations. Conclusion: Results from the current meta-analysis suggests that p53 codon 72 polymorphism might be associated with increased risk of cervical cancer, especially among Indians.

• 대한예방의학회:학술대회논문집
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• 2002.10a
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• pp.427-428
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• 2002

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7413-7417
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• 2014

Background: Development of gastric cancer (GC) is a multistep process that requires alterations in the expression of oncogenes and tumor suppressor genes, occurring over several decades. The p53 tumor suppressor protein is involved in cell-cycle control, apoptosis and DNA repair. One of the most important regulators of p53 is MDM2, which acts as a negative regulator in the p53 pathway. Based on the key role of p53 and MDM2 in tumor suppression, polymorphisms that cause change in their function might affect cancer risk. We therefore elevated associations of the polymorphisms of p53 (R72P) and MDM2 (SNP309) with GC in Iran. Materials and Methods: A total of 104 patients with gastric cancer and 100 controls were recruited. Genomic DNA was extracted from fresh gastric samples. Genotyping of the p53 and MDM2 genes was performed using allele specific PCR (AS-PCR). Results: There was no significant difference between the p53 codon 72 polymorphism distribution in control and patient groups (p=0.54), but the G allele of MDM2 was found to be over-represented in patients (p=0. 01, Odds Ratio=2. 08, 95% Confidence Interval= 1.37-4.34). Conclusions: The p53 R72P seems not to be a potential risk factor for development of GC among Iranian patients, but our data suggest that MDM2 SNP309 might modify the risk related to GC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4315-4320
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• 2012

Background: The P53 tumor suppressor gene plays a pivotal role in maintaining cellular homeostasis by preventing the propagation of genome mutations. P53 in its transcriptionally active form is capable of activating distinct target genes that contribute to either apoptosis or growth arrest, like P21. However, the MDM2 gene is a major negative regulator of P53. Single nucleotide polymorphisms (SNP) in codon Arg72Pro of P53 results in impairment of the tumor suppressor activity of the gene. A similar effect is caused by a SNP in codon 31 of P21. In contrast, a SNP in position 309 of MDM2 results in increased expression due to substitution of thymine by guanine. All three polymorphisms have been associated with increased risk of tumorigenesis. Aim of the study: We aimed to study the prevalence of SNPs in the P53 pathway involving the three genes, P53, P21 and MDM2, among acute myeloid leukemia (AML) patients and to compare it to apparently normal healthy controls for assessment of impact on risk. Results: We found that the P21 ser31arg heterozygous polymorphism increases the risk of AML (P value=0.017, OR=2.946, 95% CI=1.216-7.134). Although the MDM2 309G allele was itself without affect, it showed a synergistic effect with P21 ser/arg polymorphism (P value=0.003, OR=6.807, 95% CI=1.909-24.629). However, the MDM2 309T allele abolish risk effect of the P21 polymorphic allele (P value=0.71). There is no significant association of P53 arg72pro polymorphism on the risk of AML. Conclusion: We suggest that SNPs in the P53 pathway, especially the P21 ser31arg polymorphism and combined polymorphisms especially the P21/MDM2 might be genetic susceptibility factors in the pathogenesis of AML.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6127-6130
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• 2013

This study aimed to investigate the association between p53 Arg72Pro polymorphism and the risk of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) by conducting meta-analysis. The PubMed database was searched for relevant studies until May 30, 2013. Relevant studies were selected and data were extracted by two independent authors. Overall, subgroup, and sensitivity analyses were then conducted using the Comprehensive Meta-Analysis v2.2 software. Wild-genotype ArgArg was considered as reference [odds ratio (OR) = 1.00]. Nine studies involving 1071 HNSCC cases were obtained. Meta-analysis results indicated no association between p53 Arg72Pro polymorphism and the risk of HPV-related HNSCC: for Pro/Pro vs. Arg/Arg, OR = 1.17, 95% confidence interval (CI) = 0.70-1.98; for Arg/Pro vs. Arg/Arg, OR = 1.25, 95% CI = 0.97-1.72; and for (Pro/Pro + Arg/Pro) vs. Arg/Arg, OR = 1.28, 95% CI = 0.95-1.70. These meta-analysis results were supported by subgroup and sensitivity analysis results. In conclusions, p53 Arg72Pro polymorphism is a potential marker of HP infection-related HNSCC rather than a susceptibility gene polymorphism.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2971-2974
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• 2015

TP53 is assumed to be a very important tumour suppressor gene, as illustrated by recent reports that have shown effects of its polymorphisms on breast cancer risk. Arg72Pro and PIN3(16bp duplication) polymorphisms are proposed to have an effective role in structural changes of p53 and have therefore attracted interest as a risk factor for breast cancer in different populations. The aim of this study was to examine and determine whether p53 codon 72 and PIN3 Ins16 bp may be associated with an increased risk for breast cancer in female patients from the northwest of Iran. Genotyping was performed by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method for a total of 100 women with breast cancer and 100 healthy women without any background of cancer, focusing on the TP53 Arg72Pro-16Del/Ins haplotypes and the combined genotypes. The results in this study established no statistical significant distinctions between the genotypes and a llele frequency were found for Arg72Pro and PIN3 Ins 16 bp polymorphisms between patients and controls.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8239-8245
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• 2016

The p53 gene is inactivated by the human papillomavirus (HPV) E6 protein in the majority of cervical cancers. Treatment of HeLa S3 cells with siRNA for HPV E6 permitted adenovirus-mediated transduction of a p53 gene linked to an upstream estrogen response element (ERE). Our previous study in non-siRNA treated HHUA cells, which are derived from an endometrial cancer and express estrogen receptor ${\beta}$, showed enhancing effects of an upstream ERE on adenovirus-mediated p53 gene transduction. In HeLa S3 cells treated with siRNA for HPV E6, adenovirus-mediated transduction was enhanced by an upstream ERE linked to a p53 gene carrying a proline variant at codon 72, but not for a p53 gene with arginine variant at codon 72. Expression levels of p53 mRNA and Coxsackie/adenovirus receptor (CAR) mRNA after adenovirus-mediated transfer of an ERE-linked p53 gene (proline variant at codon 72) were higher compared with those after non-ERE-linked p53 gene transfer in siRNA-treated HeLa S3 cells. Western blot analysis showed lower ${\beta}$-tubulin levels and comparatively higher p53/${\beta}$-tubulin or CAR/${\beta}$-tubulin ratios in siRNA-treated HeLa S3 cells after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with those in non-siRNA-treated cells. Apoptosis, as measured by annexin V binding, was higher after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with that after non-ERE-linked p53 gene transfer in siRNA-treated cells.

• 대한예방의학회:학술대회논문집
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• 1999.10a
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• pp.1-15
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• 1999

In a case-control study to evaluate the factors involved in the development of hepatocellular carcinoma, polymorphisms of the p53 gene were compared in 68 cases mostly infected with hepatitis C virus (HCV) and 68 controls matched for sex and age: DNA from peripheral blood leukocytes was analyzed by the polymerase chain reaction-single strand conformation polymorphism method and direct sequencing. Polymorphisms analyzed were those in exon 4 (CCC vs. CGC, Pro vs. Arg at codon 72, Al allele vs. A2 allele), intron 2 (C vs. G at nucleotide 38, Al vs. A2), intron 3 (C vs. A at nucleotide 65, Al vs. A2; absence and presence of 16 base pair repeat at nucleotides 24 to 39, Al vs. A2), intron 6 (A vs. G at nucleotide 62, Al vs. A2) and intron 7 (C and T vs. T and G at nucleotides 72 and 92, Al vs. A2). A significantly higher frequency of the allele for CCC (Pro, Al) at codon 72 of exon 4 was found in cases (39%) than in controls (26%) (p<0.05). Highly significant linkage of the polymorphisms in exon 4, intron 2, intron 3 and intron 7, and between the intron 3-16 bp duplication and polymorphism in intron 6 also was found. Matched Fair analysis showed significantly higher frequencies of certain haplotypes (1-1-1-1-2-2 or 1-1-2-1-2-1 for exon 4, intron 2, intron 3, the intron 3-16 bp duplication, intron 6 and intron 7) in cases than in controls (p=0.014, OR=2.27, 95% CI= 1.08-5.12). No preference of specific p53 polymorphisms for specific HCV genotype was detected. These findings suggest that in hepatocarcinogenesis mainly due to HCV infection, genetic factors may be involved and that genetic markers can serve as predictors of a high-risk group for hepatocarcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2747-2751
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• 2014

Background: DNA repair pathways play a crucial role in maintaining the human genome. Previous studies associated DNA repair gene polymorphisms (XPD Lys751Gln, XRCC1 Arg280His and XRCC1 Arg399Gln) with nasopharyngeal carcinoma. These non-synonymous polymorphisms may alter DNA repair capacity and thus increase or decrease susceptibility. The present study aimed to determine the genotype distribution of XPD codon 751, XRCC1 codon 280 and codon 399 polymorphisms and haplotype associations among NPC cases and controls in the Malaysian population. Materials and Methods: We selected 157 NPC cases and 136 controls from two hospitals in Kuala Lumpur, Malaysia for this study. The polymorphisms studied were genotyped by PCR-RFLP assay and allele and genotype frequenci es, haplotype and linkage disequilibrium were determined using SNPstat software. Results: For the XPD Lys751Gln polymorphism, the frequency of the Lys allele was higher in cases than in controls (94.5% versus 85.0%). For the XRCC1 Arg280His polymorphism, the frequency of Arg allele was 90.0% and 89.0% in cases and controls, respectively and for XRCC1 Arg399Gln the frequency of the Arg allele was 72.0% and 72.8% in cases and controls respectively. All three polymorphisms were in linkage disequilibrium. The odds ratio from haplotype analysis for these three polymorphisms and their association with NPC was 1.93 (95%CI: 0.90-4.16) for haplotype CGC vs AGC allele combinations. The global haplotypte association with NPC gave a p-value of 0.054. Conclusions: Our study provides an estimate of allele and genotype frequencies of XRCC1Arg280His, XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in the Malaysian population and showed no association with nasopharyngeal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9603-9606
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• 2014

Background: Endometrial cancer is the fourth most common cancer among women in developed countries. Patients with endometrial cancer may benefit from systemic chemotherapy alone or in combination with targeted therapies if the disease is clinically diagnosed prior to spread and metastasis to other organs. The aim of this study was to evaluate the prognostic role of p53 polymorphism and its correlation with tumor grade in human uterine endometrial carcinomas. Materials and Methods: A total of 75 patients with endometrial carcinomas were studied for possible mutations in exon 4 of the p53 gene using polymerase chain reaction and restricting fragment length polymorphism techniques and sequencing. Results: In recent study, The rate of homozygote genotype of pro/pro or Arg/Arg in high grade group was higher than in comparison with low grade one. In addition samples that were undigested in RFLP, showed mutation in exone 4. Conclusions: Our findings showed that high grade endometrial carcinomas are highly associated with TP53 polymorphisms in comparison with low grades.