Study of the TP53 codon 72 polymorphism in oral cancer and oral potentially malignant disorders in Argentine patients.

The aim of this work was to evaluate the prevalence of TP53Arg72Pro mutations and their possible relationship with oral carcinoma and oral potentially malignant disorders in Argentine patients. A cross-sectional study was performed on 111 exfoliated cytologies from patients with oral cancer (OC), oral potentially malignant disorders (OPMD) and controls. The TP53Arg72Pro mutations were determined using conventional PCR. We evaluated univariate and multivariate study variables, setting p < 0.05. We found: (a) a low frequency of Pro72 variant in control group and a high frequency in OC and OPMD, as well in OC and oral leukoplakia (OL) diagnosis; (b) multivariate association among the TP53CC genotype and females over 45 years with no tobacco nor alcohol habits with oral lichen planus pathology; (c) multivariate association between the TP53GC genotype and males with alcohol and tobacco habits and OC and OL pathologies. Our results showed that the wild-type Arg72variant was related to control patients and Pro72variant was related to OC and OPMD, in Argentine patients.

Association between Hepatitis C Virus Infection, p53 Phenotypes, and Gene Variants of Adenomatous Polyposis Coli in Hepatocellular Carcinomas.

OBJECTIVE: To investigate the clinical value of p53 codon 72 single nucleotide polymorphisms (SNPs) and variants of adenomatous polyposis coli (APC) in hepatocellular carcinomas (HCCs). METHODS: DNA and RNA from 51 HCCs and their matching, uninvolved liver tissues were analyzed for p53 mutations, and the methylation and expression of APC variants were determined. Proliferation of each HCC was assessed by Ki67 immunohistochemistry. The results were correlated with the demographic and clinicopathologic features and patient survival. RESULTS: Of 51 HCCs, 12% exhibited missense p53 mutations. SNP analysis of p53 codon 72 demonstrated the highest prevalence of the Arg/Arg (56%) phenotype, followed by Arg/Pro (33%) and Pro/Pro (11%). Four of five cases with the Pro/Pro phenotype were African Americans (AAs). All five cases with the Pro/Pro phenotype had hepatitis C virus (HCV) infections, a high Ki67 index, and lower median survival (15.5 months) compared to those with Arg/Arg or Arg/Pro phenotypes (32 months). The overall frequency of APC methylation was 31%, which was found predominantly in Caucasians. There was lower mRNA expression of APC variants-2 and -3 in both HCCs and corresponding adjacent, uninvolved liver tissues as compared to APC variant-1. The expression of APC variant-3, but not variants-1 and -2, was lower in HCCs relative to uninvolved tissues. Expression of all APC variants was lower in HCCs with APC methylation relative to HCCs without APC methylation, and low expression of APC variant-2 was associated with the Pro/Pro phenotype. CONCLUSIONS: These findings suggest that, for AA patients with HCCs, the p53 Pro/Pro phenotype and low expression of APC variant-2 are associated with aggressive tumor behavior, HCV infection, and poor clinical outcome.

THE P53 CODON 72 GENOTYPES IN MONGOLIAN PATIENTS WITH RENAL CELL CARCINOMA / Мэс засал

Introduction: It has been suggested thatthe p53 codon 72 genotype is frequentlymutated in many forms of human carcinomas;however, as for renal cell carcinoma (RCC),not all investigations have been consistentand this hypothesized association remainscontroversial. These conflicting resultsmay have arisen due to different patientsubgroups and ethnicities studied. For thefirst time, this study explores the p53 codon72 genotype on Mongolian patients withRCC.Materials and methods: Genomic DNAwas obtained from the peripheral bloodsamples of 87 patients with RCC and 87 ageand gender matched cancer-free Mongolianpeople. p53 codon 72 genotyping wasexamined by PCR-RFLP. The association ofeach genotype with RCC was calculated bythe odds ratio and 95% confidence interval.Results: The proportions of the p53codon 72 genotype of 87 Mongolian patientswith RCC were Arg/Arg 57.5%, Arg/Pro26.4% and Pro/Pro16.1% respectively. Thegenotype proportions of the cancer-freeMongolian people were Arg/Arg50.6%,Arg/Pro 35.6%, Pro/Pro 13.8%, respectively.Compared to the RR genotype, odds ratioand 95% confidence interval of the PR andPP genotypes were OR=0.652 (95% CI. 0.70-0.85; p=0.997) and OR=1.026 (95% CI.0.55-0.71; p=0.998), respectively. Averageages at diagnosis for RCC patients wereRR=49±11.7, PR=51±16.2 and PP=57±12.7respectively.Conclusion: The results indicate thatArg/Arg genotype is the most common genotypein Mongolian patients with RCC and cancerfreepeople. Moreover, current sample sizesuggests thatPro/Pro (PP) genotype of thep53 codon 72 may be associated with therisk of RCC among Mongolians. There wasnot significant difference in average onsetages at diagnosis.

Role of p53 Codon72 SNP in breast cancer risk and anthracycline resistance.

BACKGROUND/AIM: We undertook a case-control and a case-case study to examine the possible association of p53 codon72 polymorphism with the breast cancer risk and resistance to anthracycline-based chemotherapy. PATIENTS AND METHODS: Case-control study: This study enrolled 175 patients with breast cancer treated at the Salah Aziez Institute and 159 healthy Tunisian women (matched for age, ethnicity and origin), used as a control, with no clinical evidence of any neoplastic disorder. Case-Case study: 400 breast cancer patients, with invasive ductal carcinoma (IDC) treated with anthracycline based-chemotherapy. Genomic DNA was isolated from whole-blood leucocytes using the phenol-chloroform method. Anthracycline response was scored according to the World Health Organization (WHO) criteria. P53 codon72 polymorphism was genotyped using real-time polymerase chain reaction (RT-PCR) with the TaqMan method. Data were statistically analyzed using the Chi-square test. RESULTS: Clinical data revealed that among the 400 patients, one quarter was resistant to chemotherapy treatment. Genetic data revealed that the p53 Arg72Pro genotype was found to be greatly associated with breast cancer risk (p<0.001), as well as tumor site (p=0.046). However, resistance to anthracycline-based chemotherapy does not seem to be correlated with p53 codon72 polymorphism in our population. Also, the distribution of tumor size, lymph node involvement and tumor grade was not significantly different among the polymorphic variants. CONCLUSION: We conclude that p53 codon72 polymorphism is involved in susceptibility to developing breast cancer. It may be a factor of progression when breast sites are taken into account. However, there is no evidence indicating that Arg72Pro SNP may influence response to anthracycline-based chemotherapy.

Allelic frequencies of p53 codon 72 polymorphism and human papillomavirus-mediated cervical cancer In Papua New Guinean women

Cervical cancer is regarded as a sexually transmitted disease caused by the human papilloma virus (HPV) detected in up to 80 per cent of the cancer biopsies. Genetic susceptibility of a p53 allelic variant has been postulated to play a vital role in carcinogenesis. This study was aimed at determining the allelic frequencies of p53 codon 72 polymorphism in Papua New Guinean women and also assessing the presence of HPV in cervical cancer biopsies. Peripheral blood (3-5 mL) was collected from 53 healthy females of reproductive age (19-37 years) with no known past and current history of HPV infections. Sixty-two cervical biopsies along with cervical swaps were obtained from patients (19-54 years) with clinical symptoms and histopathological confirmation of cervical cancer. DNA was extracted from the peripheral blood samples and cervical samples. Exon 4 was amplified with PCR and further genotypic analyses performed by Restriction fragment length polymorphism (RFLP) and single-stranded conformational polymorphism (SSCP). Of the 53 normal samples analyzed, 3.8 % (2/53) were Arginine homozygous, 58.5 % were Proline homozygous and 37.7 % were heterozygous. For the cancer samples, 14.5 % (9/62) were Arginine homozygous, 54.8 % were Proline homozygous and 30.7% were heterozygous. HPV genome was detected in 83.9 % (52/62) of the cervical cancer samples. The genotypic trend and allelic frequencies were consistent with literature.

The p53 Codon 72 Polymorphism Modifies the Cellular Response to Inflammatory Challenge in the Liver.

The p53 protein is a critical stress-response mediator and signal coordinator in cellular metabolism and environmental exposure to deleterious agents. In human populations, the p53 gene contains a common single nucleotide polymorphism (SNP) affecting codon 72 that determines whether a proline (P72) or an arginine (R72) is present at this amino acid position of the polypeptide. Previous studies carried out using human populations, mouse models, and cell culture analyses have provided evidence that this amino acid difference can alter p53 functional activities, and potentially also can affect clinical presentation of disease. The clinical presentation associated with many forms of liver disease is variable, but few of the responsible underlying genetic factors or molecular pathways have been identified. The aim of the present study was to investigate whether the p53 codon 72 polymorphism influences the cellular response to hepatic stresses. A humanized p53 knock-in (Hupki) mouse model was used to address this issue. Mice expressing either the P72 or R72 normal variation of p53 were given an acute-, intermittent- or a chronic challenge, associated with exposure to lipopolysaccharide, D-galactosamine, or a high-fat diet. The results reveal that the livers of the P72 and R72 mice exhibit notable differences in inflammatory and apoptotic response to these distinct forms of stress. Interestingly the influence of this polymorphism on the response to stress is context dependent, with P72 showing increased response to liver toxins (lipopolysaccharide and D-galactosamine), but R72 showing increased response to metabolic stress (high fat diet). When taken together, these data point to the p53 codon 72 polymorphism as an important molecular mediator of events contributing to hepatic inflammation and metabolic homeostasis.

Gastric Cancer Susceptibility in the P53 Codon 72 Polymorphism

Purpose: The P53 codon 72 polymorphism results in either arginine or proline, there are many studies to clear the relationship between P53 codon 72 genotypes and specific cancer risk and susceptibility. The purpose of this study was to investigate the association of the genotype distribution of the P53 codon 72 polymorphism and gastric cancer susceptibility via in comparison of gastric cancer group and normal control genotypes. We also studied the relation between the distribution of P53 codon 72 genotypes and the state of P53 immunohistochemical staining, infectivity of Helicobacter pylori (H.pylori) and the clinicopathologic findings in gastric cancer patients. METHODS: In our study, the samples consisted of 145 gastric cancer patients and 77 normal controls. The analysis was performed by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) method using DNA extracted from gastric cancer patients blood and normal controls blood. RESULTS: The frequency of three genotypes arg/arg, arg/ pro and pro/pro in gastric cancer patients was 41.4%, 38.6% and 20.0%. In controls, it was 36.3%, 53.2% and 10.3%. There was no statistical significance (P=0.312, 0.665). There was no correlation between the frequency of the three genotypes and the state of P53 immunohistochemical staining, infectivity of H. pylori. The pro/pro homozygote was more frequent in lymph node metastasis (25.6% vs 7.3%, P= 0.026). Conclusion: The P53 codon 72 polymorphism does not contribute to gastric cancer susceptibility. The P53 codon 72 polymorphism is not associated with the state of P53 immunohistochemical staining and the infectivity of H. pylori but pro/pro genotype is associated with the lymph node metastasis in gastric cancer patients.