• Title/Summary/Keyword: p53 polymorphism

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Association Study of the Relationship between Endometriosis and Polymorphism of p53 Codon 72 (p53 Codon 72 다형성과 한국인 여성의 자궁내막증의 연관성에 관한 연구)

  • Hur, Sung-Eun;Shim, Soung-Shin;Lee, Kyung-Soon;Moon, Hye-Sung;Yu, Han-Ki;Chung, Hye-Won
    • Clinical and Experimental Reproductive Medicine
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    • v.29 no.4
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    • pp.311-315
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    • 2002
  • Objective: The present study was performed to evaluate the association o f p53 codon 72 polymorphism and endometriosis. Materials and Methods: We investigate 74 women who were operated for endometriosis and 93 women who had no endometriotic lesion proved by operation. Polymerase chain reaction was used to detect p53 codon polymorphisms. Result: We have found no significant difference between endometriosis and control group in the p53 codon polymorphism. The respective proportion of arginine homozygotes, heterozygotes and proline homozygotes in endometriosis group were 18.9%, 62.2% and 18.9%, respectively, and were 12.9%, 75.2% and 11.9%, respective in the group without endometriosis. Conclusion: Endometriosis is not associated with p53 polymorphism in Korean endometriosis patients.

MDM2 T309G has a Synergistic Effect with P21 ser31arg Single Nucleotide Polymorphisms on the Risk of Acute Myeloid Leukemia

  • Ebid, Gamal T.;Sedhom, Iman A.;El-Gammal, Mosaad M.;Moneer, Manar M.
    • 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.

Helicobacter pylori Infection and a P53 Codon 72 Single Nucleotide Polymorphism: a Reason for an Unexplained Asian Enigma

  • Pandey, Renu;Misra, Vatsala;Misra, Sri Prakash;Dwivedi, Manisha;Misra, Alok
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9171-9176
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    • 2014
  • Aim: P53, the most commonly mutated tumor suppressor gene in all types of human cancer, is involved in cell cycle arrest and control of apoptosis. Although p53 contains several polymorphic sites, the codon 72 polymorphism is by far more common. There are divergent reports but many studies suggest p53 pro/pro SNP may be associated with susceptibility to developing various cancers in different regions of the world. The present study aimed to find any correlation between H. pylori infection and progression of carcinogenesis, by studying apoptosis and the p53 gene in gastric biopsies from north Indian population. Materials and Methods: A total of 921 biopsies were collected and tested for prevalence of H. pylori by rapid urease test (RUT), imprint cytology and histology. Apoptosis was studied by the TUNEL method. Analysis of p53 gene polymorphism at codon 72 was accomplished by PCR using restriction enzyme BstU1. Observation: Out of 921 samples tested 56.7% (543) were H. pylori positive by the three techniques. The mean apoptotic index (AI) in the normal group was 2.12, while gastritis had the maximum 4.24 followed by gastric ulcer 2.28, gastropathy 2.22 and duodenal ulcer 2.08. Mean AI in cases with gastric cancer (1.72) was less than the normal group. The analysis of p53 72 SNP revealed that p53 (Arg/Arg), (Pro /Arg) variant are higher (40.59% & 33.66%) as compared to p53 pro/pro variant (25.74%) inthe healthy population. Conclusions: The North Indian population harbors Arg or Pro/Arg SNP that is capable of withstanding stress conditions; this may be the reason of low incidence of gastric disease in spite of high infection with H. pylori. There was no significant association with H. pylori infection and AI. However, there is increased apoptosis in gastritis which may occur independent of H. pylori or p53 polymorphism.

P53 Polymorphism at Codon 72 is Associated with Keratocystic Odontogenic Tumors in the Thai Population

  • Yanatatsaneejit, Pattamawadee;Boonsrang, Ajaree;Mutirangura, Apiwat;Patel, Vyomesh;Kitkumthorn, Nakarin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1997-2001
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    • 2015
  • Objective: To clarify the association between the p53 polymorphism at codon 72 and susceptibility to the sporadic keratocystic odontogenic tumor (KCOT). Design: One hundred KCOTs and 160 match-group healthy controls were genotyped to ascertain the frequency of the p53 codon 72 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), confirmed by direct sequencing. Results: The frequencies of the Pro/Pro, Arg/Pro, and Arg/Arg genotypes were 23.8%, 49.4%, and 26.9%, respectively, in the controls, while the KCOT cohort demonstrated 43.0%, 39.0%, and 18.0%, respectively. Further analysis suggested that p53 Pro could be a KCOT-susceptible allele (OR (95%CI)=1.77 (1.22 to 2.59), p=0.0024), with a sex-adjusted OR (95%CI) of 1.71 (1.17-2.50), p=0.0046. Moreover, the results indicated that p53 codon 72 Pro homozygous was associated with a two-fold risk of developing KCOT (adjusted OR (95%CI) =2.17(1.23-3.84), p=0.0062). Conclusions: The C/C genotype of P53 gene codon 72 increases the risk of developing sporadic KCOT and may be a useful tool for screening and diagnostic purposes.

Association of a p53 Codon 72 Gene Polymorphism with Environmental Factors and Risk of Lung Cancer: a Case Control Study in Mizoram and Manipur, a High Incidence Region in North East India

  • Saikia, Bhaskar Jyoti;Das, Mandakini;Sharma, Santanu Kumar;Sekhon, Gaganpreet Singh;Zomawia, Eric;Singh, Yanglem Mohen;Mahanta, Jagadish;Phukan, Rup Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10653-10658
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    • 2015
  • Background: A very high incidence of lung cancer is observed in Mizoram and Manipur, North East India. We conducted a population based case control study to establish associations of p53 codon 72 polymorphisms and interactions with environmental factors for this high incidence. Material and Methods: A total of 272 lung cancer cases and 544 controls matched for age (${\pm}5years$), sex and ethnicity were collected and p53 codon 72 polymorphism genotypes were analyzed using a polymerase chain based restriction fragment length polymorphism assay. We used conditional multiple logistic regression analysis to calculate adjusted odds ratios and 95% confidence intervals after adjusting for confounding factors. Results: p53 Pro/Pro genotype was significantly associated with increased risk of lung cancer in the study population (adjusted OR=2.14, CI=1.35-3.38, p=0.001). Interactions of the p53 Pro/Pro genotype with exposure to wood smoke (adjusted OR=3.60, CI=1.85-6.98, p<0.001) and cooking oil fumes (adjusted OR=3.27, CI=1.55-6.87, p=0.002), betel quid chewing (adjusted OR=3.85, CI=1.96-7.55, p<0.001), tobacco smoking (adjusted OR=4.42, CI=2.27-8.63, p<0.001) and alcohol consumption (adjusted OR=3.31, CI=1.10-10.03, p=0.034) were significant regarding the increased risk of lung cancer in the study population. Conclusions: The present study provided preliminary evidence that a p53 codon 72 polymorphism may effect lung cancer risk in the study population, interacting synergistically with environmental factors.

Polymorphism of p53 Gene Codon 72 in Endometrial Cancer: Correlation with Tumor Grade and Histological Type

  • Kafshdooz, Taiebeh;Tabrizi, Ali Dastranj;Ardabili, Seyyed Mojtaba Mohaddes;Kafshdooz, Leila;Ghojazadeh, Morteza;Gharesouran, Jalal;Abdii, Ali;Alizadeh, Hamideh
    • 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.

Association Between p53 Arg72Pro Polymorphism and the Risk of Human Papillomavirus-related Head and Neck Squamous Cell Carcinoma: A Meta-analysis

  • Xia, Ling-Yun;Zeng, Xian-Tao;Li, Cheng;Leng, Wei-Dong;Fan, Ming-Wen
    • 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.

hOGG1, p53 Genes, and Smoking Interactions are Associated with the Development of Lung Cancer

  • Cheng, Zhe;Wang, Wei;Song, Yong-Na;Kang, Yan;Xia, Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1803-1808
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    • 2012
  • This study aimed to investigate the effects of Ser/Cys polymorphism in hOGG1 gene, Arg/Pro polymorphism in p53 gene, smoking and their interactions on the development of lung cancer. Ser/Cys polymorphism in hOGG1 and Arg/Pro polymorphism in p53 among 124 patients with lung cancer and 128 normal people were detected using PCR-RFLP. At the same time, smoking status was investigated between the two groups. Logistic regression was used to estimate the effects of Ser/Cys polymorphism and Arg/Pro polymorphisms, smoking and their interactions on the development of lung cancer. ORs (95% CI) of smoking, hOGG1 Cys/Cys and p53 Pro/Pro genotypes were 2.34 (1.41-3.88), 2.12 (1.03-4.39), and 2.12 (1.15-3.94), respectively. The interaction model of smoking and Cys/Cys was super-multiplicative or multiplicative, and the OR (95% CI) for their interaction item was 1.67 (0.36 -7.78). The interaction model of smoking and Pro/Pro was super-multiplicative with an OR (95%CI) of their interaction item of 5.03 (1.26-20.1). The interaction model of Pro/Pro and Cys/Cys was multiplicative and the OR (95%CI) of their interaction item was 0.99 (0.19-5.28). Smoking, hOGG1 Cys/Cys, p53 Pro/Pro and their interactions may be the important factors leading to the development of lung cancer.

Association Between TP53 Arg72Pro Polymorphism and Hepatocellular Carcinoma Risk: A Meta-analysis

  • Xu, Chang-Tao;Zheng, Fang;Dai, Xin;Du, Ji-Dong;Liu, Hao-Run;Zhao, Li;Li, Wei-Min
    • 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.

No Evidence of Association of the Arg72Pro p53 Gene Polymorphism with Cancer Risk in the Saudi Population: a Meta-Analysis

  • Irshad, Mohammad;Mandal, Raju Kumar;Al-Drees, Abdulmajeed;Khalil, Mahmoud Salah;Abdulghani, Hamza Mohammad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5663-5667
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    • 2015
  • Background: Earlier studies on the association between p53 codon 72 Arg>Pro polymorphism and cancer risk were inconclusive and conflicting for the Saudi population. Therefore, we performed a meta-analysis to investigate the relationship between the codon 72 Arg>Pro polymorphism and overall cancer risk in Saudi Arabia. Materials and Methods: We searched all eligible published studies and data were pooled together to perform the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for homozygous, heterozygous, dominant and recessive genetic models. Results: A total of five eligible published studies covering 502 cancer cases and 784 healthy controls were included in the meta-analysis. No publication bias was detected in this study. The results suggested that the variant (Pro vs Arg: p=0.960; OR=1.004, 95% CI=0.852-1.183), homozygous (Pro.Pro vs Arg.Arg: p=0.970; OR=1.006, 95% CI=0.729-1.390), heterozygous (Arg.Pro vs Arg.Arg: p=0.473; OR=0.783, 95% CI=0.402-1.527) carriers were not associated with overall cancer risk. Similarly, dominant (Pro.Pro+Pro.Arg vs Arg.Arg: p=0.632; OR=0.886, 95% CI=0.540-1.454) and recessive (Pro.Pro vs Pro.Arg+Arg.Arg: p=0.269; OR=1.163, 95%CI=0.890-1.521) models also did not indicate increased risk of cancer. Conclusions: The current meta-analysis suggests that the codon 72 Arg>Pro polymorphism of the p53 gene might not contribute to cancer susceptibility in Saudi population. Future well designed large case control studies are needed to validate our findings.