Codon 72 polymorphism of p53 and its association with cervical cancer

doi:10.1016/S0140-6736(99)01914-5

The Lancet

Volume 354, Issue 9174, 17 July 1999, Pages 218-219

https://doi.org/10.1016/S0140-6736(99)01914-5 Get rights and content

Summary

Swedish and Italian women with HPV 16-positive cervical disease were checked for codon 72 polymorphisms of p53. In both groups, arginine homozygotes were enriched in cancer compared with controls and precursor lesions.

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There are more references available in the full text version of this article.

Cited by (130)

Correlation between P53 Arg72Pro and MDM4 gene rs4245739 polymorphisms in breast cancer
2020, Gene Reports
MDM4 is a negative regulator of p53 tumor suppression pathway. Various studies reveal the fact that the rs4245739A>C polymorphism of MDM4 in 3′-untranslated region is targeted by miR-191 which leads to lower MDM4 expression. On the other hand, the importance of Arg72Pro polymorphism of p53 in breast cancer is proven. The aim of this study is to present the correlation between the aforementioned SNPs and the risk of breast cancer. The statistical society of the study includes 199 healthy women as the control group and 206 women suffering from breast cancer included from Turkish population of the East Azarbaijan.
Alleles of both positions are detected through Tetra-ARMS PCR while SPSS and the SHEsis, online software was exerted for allele typing, genotyping, and haplotype analysis. Different alleles of both MDM4 rs4245739 and p53 Arg72Pro had no significant frequency in patients (P > 0.05). Furthermore, genotypes of neither MDM4 rs4245739 nor p53 Arg72Pro could increase or decrease the risk of breast cancer in patients compared to healthy women. Additionally, a significant factor affecting the risk of breast cancer is gene-gene interaction. The results of the ongoing study revealed that two genetic variants, MDM4 rs4245739 and p53 Arg72Pro polymorphisms, failed to be associated, individually and combined together, with the risk of breast cancer. However, additional well-designed studies on large populations are required to validate such an association.
Various alleles of both SNPs had no significant frequency difference between patients and controls. Moreover, genotypes of neither MDM4 nor p53 were significantly distributed in women with breast cancer compared to the healthy controls. Meanwhile, haplotype analysis failed to be significant. Last but not least, all clinical manifestations, other than association between tumor size and MDM4 genotypes could not be correlated with either various alleles or genotypes.
Identification of human papillomavirus-16 E6 variation in cervical cancer and their impact on T and B cell epitopes
2015, Journal of Virological Methods
The infection with high-risk human papillomavirus (HR-HPV) is the most important risk factor for development of cervical cancer. The intra-type variations of HPV have different biological and pathological consequences with respect to disease progression. In the present study, six major Indian variants were experimentally identified in E6 gene of HPV-16 and showed their impact on immunogenicity by in silico methods. Four different phylogenetic lineages were observed in sequences including European (E) prototype, European variant, Asian and American Asian variant classes and complete absence of African phylogenetic lineages. On the prediction of B- and T-cell epitopes, 18 and 23 potent epitopes for MHC-II alleles, 10 potent MHC-I and 15 B-cell epitopes in each reference and variant sequence were identified. Interestingly, the presence of variation H78Y and L83V result in creation of four new epitopes for the HLA-DQA1*0101/DQB1*0501. Out of 15 B-cell predicted epitopes, three most potent epitopes were identified in both reference and variant sequence. Notably the amino acid stretch from amino acid 16–60 and 76–94 are very important for the immunological properties of E6 protein because these regions contain majority of the predicted epitopes. In future, this could control the cervical cancer by targeting these amino acid stretches for the development of HPV-16 vaccine.
Association of p53 and MDM2 polymorphisms with risk of human papillomavirus (HPV)-related esophageal squamous cell carcinoma (ESCC)
2013, Cancer Epidemiology
Though polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous tumors, particularly tumors associated with human papillomavirus (HPV) infection. However, the results remain controversial. Our previous study showed that HPV serostatus is not an independent risk factor for esophageal squamous cell carcinoma (ESCC) in nonsmokers and nondrinkers. Given the roles of p53 and HPV E6 as well as MDM2 oncoproteins in p53 degradation, we validated the association of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.
Single nucleotide polymorphisms of p53 Arg72Pro (rs1042522) and MDM2 (rs937283) in 307 ESCC patients and 311 healthy controls were genotyped. The presence or absence of HPV16 in serum was measured by enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was used to evaluate the possible associations of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.
Patients carrying p53 Arg/Arg or Arg/Pro had a higher risk of esophageal SCC (P < 0.001, Odds ratio [OR] 4.98, 95% confidential interval [CI] 3.46–7.17), however, not found in MDM2 rs937283. The risk of esophageal SCC increased significantly among patients carrying p53 Arg/Arg, or Arg/Pro and HPV16-seropositivity (P < 0.001, OR 9.33, 95% CI 5.44–16.0), but not for MDM2 rs937283. The risk of esophageal SCC was further elevated among patients carrying Arg/Arg or Arg/Pro and HPV16-seropositivity who were smokers (P < 0.001, OR 27.05, 95% CI 11.06–66.16) or drinkers (P < 0.001, OR 13.20, 95% CI 5.74–30.38).
HPV16 seropositivity synergized with p53 Arg/Arg or Arg/Pro and increased ESCC risk, especially in smokers or drinkers.
Role of human papillomavirus and cell cycle-related variants in squamous cell carcinoma of the oropharynx
2010, Journal of Biomedical Research
The LIG4 Ile658Val polymorphism does not affect the risk of cervical carcinoma
2010, Pathology Research and Practice
The aim of this study was to investigate whether gene LIG4 genetic polymorphism affects the risk of cervical carcinoma. We studied 500 cervical carcinoma patients and 800 normal women as controls. Demographic and epidemiologic risk factors were recorded. Single nucleotide polymorphisms (SNPs) (LIG4 Ile658Val) were genotyped. Compared to LIG4 Ile658Ile (AA) genotype, LIG4 Ile658Val (AG) did not increase or decrease the risk of cervical carcinoma or cervical squamous cell carcinoma [ORs and 95% CIs being 1.07 (0.70–1.63) and 1.01 (0.65–1.55)], while no homozygous LIG4 Val658Val (GG) was found in the cervical carcinoma group. Analyzing the risk of variant LIG4 Ile658Val genotypes for cervical carcinoma of different histologic types or HPV infection status, we found striking similarities between the squamous cell carcinoma group and the HPV-positive group and the overall carcinoma. In conclusion, in the Chinese population, LIG4 Ile658Val has only a slight impact on the risk of developing cervical carcinoma.
Association of TP53 codon 72 polymorphism with cervical cancer risk in Chinese women
2010, Cancer Genetics and Cytogenetics
Polymorphism at codon 72 of TP53, resulting in either the arginine (Arg) or proline (Pro) form of p53 (R72P), has been associated with the susceptibility to different cancers. To better understand the role of this polymorphism in cervical cancer etiology, we investigated the association between p53 R72P and cervical cancer risk in Chinese women from southern Han. Blood samples from 105 women with cervical cancer and from 140 female blood donors were collected. DNA from peripheral blood lymphocytes was extracted, and the exon 4 of TP53 was amplified by polymerase chain reaction and then digested by BstUI. We observed that the Arg/Arg genotype was significantly associated with an increased risk for cervical cancer [odds ratio (OR) = 1.465, 95% confidence interval (95%CI) = 1.04–2.138, P = 0.02]. The relative frequency of each allele was 0.69 for Arg and 0.31 for Pro in patients with cervical cancer, and 0.60 for Arg and 0.40 for Pro in normal controls (P < 0.05). Furthermore, we also found that the TP53 R72P polymorphism was not linked to tumor histologic type, histologic grade, lymph node metastases, and tumor size. These findings suggest that the TP53 codon 72 polymorphism may be implicated in cervical carcinogenesis, with the Arg/Arg genotype being associated with an increased susceptibility for this malignancy in the southern Chinese population.

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Research LettersCodon 72 polymorphism of p53 and its association with cervical cancer

Summary

Lancet

Role of a p53 polymorphism in the development of human papillomavirus-associated cancer

Nature

Research Letters
Codon 72 polymorphism of p53 and its association with cervical cancer