ABSTRACT
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.
ABSTRACT
Objective:To investigate the association between p53 codon 72 polymorphism and the prognosis of breast cancer pa-tients receiving chemotherapy and radiotherapy after surgery. Methods:A total of 427 breast cancer patients treated with chemo-radio-therapy after surgery at Beijing Cancer Hospital were selected for this study. Polymerase chain reaction–restriction fragment length polymorphism was adopted to analyze the p53 codon 72 polymorphism. Survival analysis was conducted to compare the disparities of recurrence and survival among the patients with different p53 codon 72 polymorphic variants. Results:The distribution of three geno-types of p53 codon 72 in our cohort is as follows:Pro/Pro 18.3%(78/427), Pro/Arg 44.0%(188/427), and Arg/Arg 37.7%(161/427). No significant difference was observed among the local recurrence-free survival (LRFS), loco-regional recurrence-free survival (LR-RFS), distant disease-free survival (DDFS), and overall survival (OS) among the three genotypes (all P>0.05). Among the 303 estro-gen receptor (ER)-positive patients, OS was significantly better in patients with Arg/Arg genotype than those with Pro/Pro genotype (χ2=6.33, P=0.042). The multivariate analysis showed that the p53 codon 72 polymorphism is an independent factor of prognosis for LRFS, LRRFS, DDFS, and OS of ER-positive patients. For the ER positive patients with Pro/Pro genotype, the local recurrence, local-regional recurrence, distant metastasis, and mortality risks were 5.9 (HR=5.9, 95%CI 1.1-31.1, P=0.036), 3.1 (HR = 3.1, 95% CI 1.1-9.1, P=0.039), 2.8 (HR=2.8, 95% CI 1.3-6.0, P=0.010), and 4.0 (HR=4.0, 95% CI 1.3-12.0, P=0.013) times higher than those with Arg/Arg genotype, respectively. Conclusion:For ER-positive breast cancer patients who underwent surgery and chemo-radiotherapy, the local recurrence, loco-regional recurrence, distant metastasis, and mortality risk with Pro/Pro genotype are significantly higher compared to those with Arg/Arg genotype.
ABSTRACT
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.
ABSTRACT
Polymorphisms of the p53 gene, which participates in DNA repair, can affect the functioning of the p53 protein. The Arg and Pro variants in p53 codon 72 were shown to have different regulation properties of p53-dependent DNA repair target genes that can affect various levels of cytogenetic aberrations in chronic hepatitis B patients. The present study aimed to examine the frequency of chromosomal aberrations and the mitotic index in patients with chronic hepatitis B and their possible association with p53 gene exon 4 codon 72 Arg72Pro (Ex4+119 G>C; rs1042522) polymorphism. Fifty-eight patients with chronic hepatitis B and 30 healthy individuals were genotyped in terms of the p53 gene codon 72 Arg72Pro polymorphism by PCR-RFLP. A 72-h cell culture was performed on the same individuals and evaluated in terms of chromosomal aberrations and mitotic index. A high frequency of chromosomal aberrations and low mitotic index were detected in the patient group compared to the control group. A higher frequency of chromosomal aberrations was detected in both the patient and the control groups with a homozygous proline genotype (13 patients, 3 control subjects) compared to patients and controls with other genotypes [Arg/Pro (38 patients, 20 control subjects) and Arg/Arg (7 patients, 7 control subjects)]. We observed an increased frequency of cytogenetic aberrations in patients with chronic hepatitis B. In addition, a higher frequency of cytogenetic aberrations was observed in p53 variants having the homozygous proline genotype compared to variants having other genotypes both in patients and healthy individuals.
Subject(s)
Adult , Female , Humans , Male , Codon/genetics , Hepatitis B, Chronic/genetics , Polymorphism, Genetic/genetics , /genetics , Arginine/genetics , Case-Control Studies , Chromosome Aberrations , Genetic Predisposition to Disease , Genotype , Mitotic Index , Proline/geneticsABSTRACT
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.