Evaluation of p53 codon 72 polymorphism in adenocarcinomas of the colon and rectum in La Plata, Argentina

Aim: To evaluate the potential association between p53 codon 72 polymorphism and sporadic colorectal adenocarcinoma development, and human papillomavirus (HPV) infection. Methods: One-hundred and nine controls and 53 patients with colon cancer from the city of La Plata, Argentina were analyzed. p53 codon 72 genotypes and HPV infection were identified using allele-specific polymerase chain reaction and nested polymerase chain reaction, respectively. Results: The differences in the distribution of p53 codon 72 polymorphism between the cases and controls were statistically significant. The arginine allele had a prevalence of 0.65 in controls and 0.77 in cases. The corresponding odds ratio for the homozygous arginine genotype was 2.08 (95% CI, 1.06-4.05; P<0.05). Lack of association was found between p53 polymorphism and HPV infection in the set of adenocarcinomas. Conclusion: The findings of the present study indicate that p53 codon 72 arginine homozygous genotype may represent a genetic predisposing factor for colon cancer development. However, further studies are needed in order to elucidate the role of p53 codon 72 polymorphism in colorectal cancer.Facultad de Ciencias Veterinaria

Detection of human papillomavirus DNA and p53 codon 72 polymorphism in prostate carcinomas of patients from Argentina

BACKGROUND: Infections with high-risk human papillomaviruses (HPVs), causatively linked to cervical cancer, might also play a role in the development of prostate cancer. Furthermore, the polymorphism at codon 72 (encoding either arginine or proline) of the p53 tumor-suppressor gene is discussed as a possible determinant for cancer risk. The HPV E6 oncoprotein induces degradation of the p53 protein. The aim of this study was to analyse prostate carcinomas and hyperplasias of patients from Argentina for the presence of HPV DNA and the p53 codon 72 polymorphism genotype. METHODS: HPV DNA detection and typing were done by consensus L1 and type-specific PCR assays, respectively, and Southern blot hybridizations. Genotyping of p53 codon 72 polymorphism was performed both by allele specific primer PCRs and PCR-RFLP (Bsh1236I). Fischer's test with Woolf's approximation was used for statistical analysis. RESULTS: HPV DNA was detected in 17 out of 41 (41.5 %) carcinoma samples, whereas all 30 hyperplasia samples were HPV-negative. Differences in p53 codon 72 allelic frequencies were not observed, neither between carcinomas and hyperplasias nor between HPV-positive and HPV-negative carcinomas. CONCLUSION: These results indicate that the p53 genotype is probably not a risk factor for prostate cancer, and that HPV infections could be associated with at least a subset of prostate carcinomas

In B-CLL, the codon 72 polymorphic variants of p53 are not related to drug resistance and disease prognosis

BACKGROUND: A common sequence polymorphism at codon 72 of the p53 gene encoding either arginine or proline was recently shown to be functionally relevant for apoptosis induction in vitro. In B-type chronic lymphocytic leukemia (B-CLL), p53 gene mutations occur in a subset of patients and are associated with impaired survival and drug resistance. Here, we address the functional relevance of the codon 72 single nucleotide (SNP) polymorphism for cell death sensitivity following exposure to clinically employed cytotoxic drugs and gamma-irradiation. METHODS: 138 B-CLL samples were analysed by SSCP-PCR and sequencing for single nucleotide polymorphism at codon 72 of the p53 gene. The in vitro cytotoxicity assay (DiSC-assay) was performed with 7 drugs (chlorambucil, mafosfamide, fludarabine phosphate, methylprednisolone, doxorubicin, vincristine) or gamma-irradiation. RESULTS: Of the 138 B-CLL samples, 9 samples were homozygous for proline (Pro/Pro), 78 samples homozygous for arginine (Arg/Arg), and 49 samples heterozygous (Arg/Pro). No differences were found for patient survival and cell death triggered by 7 cytotoxic drugs or gamma-irradiation. CONCLUSION: These data indicate that polymorphic variants of p53 codon 72 are not clinically relevant for apoptosis induction or patient survival in B-CLL

Evaluation of p53 codon 72 polymorphism in adenocarcinomas of the colon and rectum in La Plata, Argentina

Aim: To evaluate the potential association between p53 codon 72 polymorphism and sporadic colorectal adenocarcinoma development, and human papillomavirus (HPV) infection. Methods: One-hundred and nine controls and 53 patients with colon cancer from the city of La Plata, Argentina were analyzed. p53 codon 72 genotypes and HPV infection were identified using allele-specific polymerase chain reaction and nested polymerase chain reaction, respectively. Results: The differences in the distribution of p53 codon 72 polymorphism between the cases and controls were statistically significant. The arginine allele had a prevalence of 0.65 in controls and 0.77 in cases. The corresponding odds ratio for the homozygous arginine genotype was 2.08 (95% CI, 1.06-4.05; P<0.05). Lack of association was found between p53 polymorphism and HPV infection in the set of adenocarcinomas. Conclusion: The findings of the present study indicate that p53 codon 72 arginine homozygous genotype may represent a genetic predisposing factor for colon cancer development. However, further studies are needed in order to elucidate the role of p53 codon 72 polymorphism in colorectal cancer.Facultad de Ciencias Veterinaria

Association of p53 Codon 72 Polymorphism with Risk of Hypopharyngeal Squamous Cell Carcinoma in Taiwan

Backgroundp53 polymorphism at codon 72 is a known risk marker for various malignancies, but it has not been studied in hypopharyngeal cancer. This study investigated the genotype distribution of p53 codon 72 polymorphism in hypopharyngeal cancer patients and non-cancer controls matched for age, gender, alcohol consumption and smoking habit.MethodsGenomic DNA was extracted from peripheral blood cells of 53 patients with hypopharyngeal cancer and 53 non-cancer controls. Codon 72 polymorphism of p53 was identified by polymerase chain reaction-restriction fragment length polymorphism.ResultsPatients with hypopharyngeal cancer had higher frequencies of Pro/Pro (26.4% vs. 13.2%) and Pro/Arg (51.0% vs. 45.3%) but lower frequencies of Arg/Arg (22.6% vs. 45.1%) compared to controls. Compared to Arg/Arg genotypes, Pro/Pro genotypes had a relative risk of hypopharyngeal cancer of 3.667 (95% confidence interval, 1.16-11.56; p = 0.03). As a group, patients with Pro/Pro or Arg/Pro who were carriers of the Pro allele had a higher relative risk of hypopharyngeal cancer compared to Arg homozygous carriers (odds ratio, 2.415; 95% confidence interval, 1.04-5.64; p = 0.04).ConclusionThis study demonstrated that p53 codon 72 Pro homozygosity is associated with a higher risk of developing hypopharyngeal cancer

Association of the p53 Codon 72 Polymorphism with Colorectal Cancer in South West of Iran

Abstract—The p53 tumor suppressor gene plays two important roles in genomic stability: blocking cell proliferation after DNA damage until it has been repaired, and starting apoptosis if the damage is too critical. Codon 72 exon4 polymorphism (Arg72Pro) of the P53 gene has been implicated in cancer risk. Various studies have been done to investigate the status of p53 at codon 72 for arginine (Arg) and proline (Pro) alleles in different populations and also the association of this codon 72 polymorphism with various tumors. Our objective was to investigate the possible association between P53 Arg72Pro polymorphism and susceptibility to colorectal cancer among Isfahan and Chaharmahal Va Bakhtiari (a part of south west of Iran) population. We investigated the status of p53 at codon 72 for Arg/Arg, Arg/Pro and Pro/Pro allele polymorphisms in blood samples from 145 colorectal cancer patients and 140 controls by Nested-PCR of p53 exon 4 and digestion with BstUI restriction enzyme and the DNA fragments were then resolved by electrophoresis in 2% agarose gel. The Pro allele was 279 bp, while the Arg allele was restricted into two fragments of 160 and 119 bp. Among the 145 colorectal cancer cases 49 cases (33.79%) were homozygous for the Arg72 allele (Arg/Arg), 18 cases (12.41%) were homozygous for the Pro72 allele (Pro/Pro) and 78 cases (53.8%) found in heterozygous (Arg/Pro). In conclusion, it can be said that p53Arg/Arg genotype may be correlated with possible increased risk of this kind of cancers in south west of Ira

Effects of MDM2, MDM4 and TP53 Codon 72 Polymorphisms on Cancer Risk in a Cohort Study of Carriers of TP53 Germline Mutations

Previous studies have shown that MDM2 SNP309 and p53 codon 72 have modifier effects on germline P53 mutations, but those studies relied on case-only studies with small sample sizes. The impact of MDM4 polymorphism on tumor onset in germline mutation carriers has not previously been studied.We analyzed 213 p53 germline mutation carriers including 168(78.9%) affected with cancer and 174 who had genotypic data. We analyzed time to first cancer using Kaplan-Meier and Cox proportional hazards methods, comparing risks according to polymorphism genotypes. For MDM2 SNP309, a significant difference of 9.0 years in the average age of cancer diagnosis was observed between GG/GT and TT carriers (18.6 versus 27.6 years, P = 0.0087). The hazards ratio was 1.58 (P = 0.03) comparing risks among individuals with GG/GT to risk among TT, but this effect was only significant in females (HR = 1.60, P = 0.02). Compared to other genotypes, P53 codon 72 PP homozygotes had a 2.24 times (P = 0.03) higher rate for time to develop cancer. We observed a multiplicative joint effect of MDM2 and p53 codon72 polymorphism on risk. The MDM4 polymorphism had no significant effects.Our results suggest that the MDM2 SNP309 G allele is associated with cancer risk in p53 germline mutation carriers and accelerates time to cancer onset with a pronounced effect in females. A multiplicative joint effect exists between the MDM2 SNP309 G allele and the p53 codon 72 G allele in the risk of cancer development. Our results further define cancer risk in carriers of germline p53 mutations

Association of the p53 codon 72 polymorphism with breast cancer in central part of Iran

The tumor suppressor gene protein 53 (p53) plays a general role in cell cycle control, the initiation of apoptosis and in DNA repair. The human p53 gene is mutated and accumulated in more than 50% of cancers. Codon 72 exon 4 polymorphism (Arg72Pro) of the p53 gene has been implicated in cancer risk. This study was aimed at investigating the possible association between p53 Arg72Pro polymorphism and susceptibility to breast cancer among Iranian population. The p53 Arg72Pro genotypes were determined by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) analysis in 135 breast cancer cases and 150 controls. The PCR products were digested with BstU I restriction enzyme and the DNA fragments were then resolved by electrophoresis in 2% agarose gel. Out of the 135 breast cancer samples, 102 (75.55 %) samples were heterozygous (Arg/Pro), 27 (20%) samples homozygous for arginine (Arg/Arg) and 6 (4.45%) samples homozygous for proline (Pro/Pro). The frequencies of the three p53 genotypes; Arg/Pro, Arg/Arg and Pro/Pro in controls were 62, 24 and 14%, respectively. Heterozygosity for Arg/Pro of p53 codon 72 is potentially one of the genetic risk factors for breast cancer. The p53 Arg72Pro polymorphism may be used as a stratification marker in screening individuals at a high risk of breast cancer

The p53 codon 72 polymorphism and association to prostate cancer in Iranian patients

Tp53 is an important tumor suppressor gene, which induces cell growth arrest or apoptosis when subjected to cytotoxic stimuli. Association has been reported between various cancers and p53 codon 72 polymorphism. Our objective was to investigate the possible association between p53 at codon 72 for Arg/Arg, Arg/Pro and Pro/Pro allele polymorphisms in blood samples from 187 prostate cancer patients and 185 controls in southwest Iran by nested-polymerase chain reaction (PCR) of p53 exon 4 and digestion with BstUI restriction enzyme and the DNA fragments were then resolved by electrophoresis in 2% agarose gel. The frequencies of Arg/Arg, Arg/Pro and Pro/Pro genotypes were 39.57% (74/187), 52.41% (98/187) and 8.02% (15/187), respectively, in the cases with prostate cancer, and 27.03% (50/185), 60% (111/185) and 12.97% (24/185), respectively in the healthy controls. Statistically, analyzed and combined results showed there was a significant difference in the frequency of the Arg/Arg genotype and Arg allele between prostate cancer cases and control (p&gt;0.001). These findings suggest that p53 Arg/Arg genotype could be a risk factor for the development of prostate cancer among patients in southwest Iran.Key words: Prostate cancer, suppressor gene (p53) codon 72, polymorphism, Iran