Tp53 codon‐72 polymorphisms identify different radiation sensitivities to g2‐chromosome breakage in human lymphoblast cells

Schwartz, Jeffrey L.; Plotnik, David A.; Slovic, Jana; Li, Tiffany; Racelis, Maximillian; Deeg, H. Joachim; Friedman, Debra L.

doi:10.1002/em.20635

Cited by 9 publications

(8 citation statements)

References 25 publications

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“…Another study by Alsbeih et al in 2007 also revealed a similar result, namely that the variant TP53 Arg72 allele was associated with a decrease in radiosensitivity [35]. A study by Schwartz et al in 2011 using the human lymphoblast cells revealed that cell lines with homozygous Proline coding allele were more likely to be resistant to radiation-induced chromatid break formation in G 2 chromosomal radiosensitivity assay compared to those containing two arginine coding alleles [36]. Another study by Pereira et al in 2011 revealed that the homozygous arginine coding alleles increase the number of cells with karyorrhexis in buccal cells of head and neck cancer patients after the first session of radiotherapy [37].…”

Section: Association Between Tp53 Arg72pro Polymorphism and Radiosensmentioning

confidence: 87%

Assessment of Individual Radiosensitivity in Inhabitants of Takandeang Village － A High Background Radiation Area in Indonesia

et al. 2019

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People living in high background radiation areas (HBRAs) possibly develop the radioadaptive response (RAR) phenomenon. The Mamuju area in West Sulawesi Indonesia is known as an HBRA in Indonesia due to its high natural uranium contents. It is possible that RAR has developed in Mamuju inhabitants. To prove this hypothesis, here in this study, evaluation of the individual radiosensitivity in the inhabitants of Takandeang Village, Mamuju, was conducted using G 2 micronucleus (MN) assay. Association between blood groups and TP53 Arg72Pro polymorphism with individual radiosensitivity was also evaluated in this study. Using G 2 MN assay, we assessed the individual radiosensitivity of Takandeang Village inhabitants and control samples. For each sample, three parameters were calculated. The spontaneous (baseline) MN number, MN number after 0.5 Gy in vitro irradiation, and radiation-induced MN were calculated to predict the individual radiosensitivity. The radiation-induced MN was defined by subtracting the spontaneous MN number from the MN number after irradiation. The mean and SD of the number of micronuclei induced by radiation found in control group (CG) was set as the cutoff value to determine the individual radiosensitivity in all samples. The occurrence of a radiation-induced MN value higher than the mean CG + 1SD CG was scored as 1, indicating a milder radiosensitive phenotype, whereas a result higher than the mean CG + 2SD CG was scored as 2, and indicated a more severe radiosensitive phenotype. When the individual value was lower than the mean CG + 1SD CG, a score of 0 was attributed to the tested subject. The results showed that four individuals in Takandeang Village inhabitants had a milder radiosensitive phenotype, while the others were categorized as normal radiosensitive. A similar finding was also found in control samples. Our study failed to find any correlation between radiosensitivity and either blood group or the TP53 Arg72Pro polymorphism. Overall, our study revealed the possibility of RAR phenomena in Takandeang Village inhabitants. Further investigation using a different point of radiation dose value and larger sample number should be performed to validate this study results.Journal homepage: http://aij.batan.go.id

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Section: Association Between Tp53 Arg72pro Polymorphism and Radiosensmentioning

confidence: 87%

Assessment of Individual Radiosensitivity in Inhabitants of Takandeang Village － A High Background Radiation Area in Indonesia

et al. 2019

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“…Later, Litviakov 33 showed that cancer patients with Pro/Pro genotype have fewer chromatid breaks in comparison to Arg/Pro and Arg/Arg carriers. Moreover, chromosomal radiosensitivity, as measured by the G2-chromosome break assay, has been reported to be associated with polymorphisms in TP53 codon 72 34 . In that study, reduced frequencies of radiation-induced chromatid aberrations were observed in normal human lymphoblast cell lines with the Pro/Pro genotype compared to other genotypes.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in MDM2 and TP53 Genes and Risk of Developing Therapy-Related Myeloid Neoplasms

Cabezas

Garcia-Quevedo

Alonso

et al. 2019

Sci Rep

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One of the most severe complications after successful cancer therapy is the development of therapy-related myeloid neoplasms (t-MN). Constitutional genetic variation is likely to impact on t-MN risk. We aimed to evaluate if polymorphisms in the p53 pathway can be useful for predicting t-MN susceptibility. First, an association study revealed that the Pro variant of the TP53 Arg72Pro polymorphism and the G allele of the MDM2 SNP309 were associated with t-MN risk. The Arg variant of TP53 is more efficient at inducing apoptosis, whereas the Pro variant is a more potent inductor of cell cycle arrest and DNA repair. As regards MDM2 SNP309, the G allele is associated with attenuation of the p53 apoptotic response. Second, to evaluate the biological effect of the TP53 polymorphism, we established Jurkat isogenic cell lines expressing p53Arg or p53Pro. Jurkat p53Arg cells presented higher DNA damage and higher apoptotic potential than p53Pro cells, after treatment with chemotherapy agents. Only p53Pro cells presented t(15;17) translocation and del(5q). We suggest that failure to repair DNA lesions in p53Arg cells would lead them to apoptosis, whereas some p53Pro cells, prone to cell cycle arrest and DNA repair, could undergo misrepair, generating chromosomal abnormalities typical of t-MN.

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“…A common Tp53 polymorphism located at codon 72 (encoding either a proline or arginine residue), within a conserved proline rich SH3 binding domain, is known to be critical for promoting apoptosis [33], [34], and laboratory based studies have demonstrated functional and biologic differences between the two polymorphic forms [35], [36], [37], [38], [39], [40], [41]. The codon 72 polymorphism has a well-characterized geographic distribution, with the frequency of Tp53-72R increasing with geographic distance from the equator.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Tp53 Codon 72 Polymorphisms, Tp53 Mutations, and HPV Infection in Cutaneous Squamous Cell Carcinomas

et al. 2012

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BackgroundNon-melanoma skin cancers are one of the most common human malignancies accounting for 2–3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers. In this study we assessed the association of HPV infection and Tp53 polymorphisms and mutations in lesional specimens with squamous cell carcinomas.MethodsWe studied 55 cases of histologically confirmed cutaneous squamous cell carcinoma and 41 controls for the presence of HPV infection and Tp53 genotype (mutations and polymorphism).ResultsWe found an increased number of Tp53 mutations in the squamous cell carcinoma samples compared with perilesional or control samples. There was increased frequency of homozygous Tp53-72R polymorphism in cases with squamous cell carcinomas, while the Tp53-72P allele (Tp53-72R/P and Tp53-72P/P) was more frequent in normal control samples. Carcinoma samples positive for HPV showed a decreased frequency of Tp53 mutations compared to those without HPV infection. In addition, carcinoma samples with a Tp53-72P allele showed an increased incidence of Tp53 mutations in comparison carcinomas samples homozygous for Tp53-72R.ConclusionsThese studies suggest there are two separate pathways (HPV infection and Tp53 mutation) leading to cutaneous squamous cell carcinomas stratified by the Tp53 codon-72 polymorphism. The presence of a Tp53-72P allele is protective against cutaneous squamous cell carcinoma, and carcinoma specimens with Tp53-72P are more likely to have Tp53 mutations. In contrast Tp53-72R is a significant risk factor for cutaneous squamous cell carcinoma and is frequently associated with HPV infection instead of Tp53 mutations. Heterozygosity for Tp53-72R/P is protective against squamous cell carcinomas, possibly reflecting a requirement for both HPV infection and Tp53 mutations.

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Tp53 codon‐72 polymorphisms identify different radiation sensitivities to g2‐chromosome breakage in human lymphoblast cells

Cited by 9 publications

References 25 publications

Assessment of Individual Radiosensitivity in Inhabitants of Takandeang Village － A High Background Radiation Area in Indonesia

Assessment of Individual Radiosensitivity in Inhabitants of Takandeang Village － A High Background Radiation Area in Indonesia

Polymorphisms in MDM2 and TP53 Genes and Risk of Developing Therapy-Related Myeloid Neoplasms

Analysis of Tp53 Codon 72 Polymorphisms, Tp53 Mutations, and HPV Infection in Cutaneous Squamous Cell Carcinomas

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