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

Cabezas, María Dolores Chaparro; Garcia-Quevedo, L.; Alonso, Cintia; Manubens, Marta; Álvarez, Yolanda; Barquinero, Joan Francesc; Cajal, Santiago Ramón y; Ortega, Margarita; Blanco, Adoración; Caballı́n, Marı́a Rosa; Armengol, Gemma

doi:10.1038/s41598-018-36931-x

Cited by 6 publications

(6 citation statements)

References 46 publications

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“…The variant allele of MDM2 rs2279744 enhances the risk effect of the variant allele of TP53 rs1042522. MDM2 rs2279744 and TP53 rs1042522 interaction and their association with the risk for cancer were recently reported by Cabezas M et al [29] in therapy-related myeloid neoplasms. Our results are explained by the fact that TP53 rs1042522 variant allele was reported to modify the p53 function and interaction with MDM2 protein [42], thus being reported by several studies as a risk factor for cancer.…”

Section: Discussionsupporting

confidence: 52%

“…MDM2 rs2279744 (MDM2 309T>G) and rs3730485 (MDM2 del1518) and MDM4 rs4245739 (MDM4 34091 C>A) variants were reported to influence the genes activity being associated with carcinogenesis and tumor progression [17][18][19][20]. Moreover, the interaction between TP53 rs1042522 and MDM2 rs2279744 [11,13,29] and between MDM2 rs2279744 and rs3730485 [21] was reported. Therefore, our study evaluated the associations between the mentioned variants and odds of developing AML and the interactions of investigated TP53, MDM2, and MDM4 variants and their association with odds of AML.…”

Section: Discussionmentioning

confidence: 99%

“…In other hematological malignancies, such as chronic lymphoid leukemia, the variant genotype of rs2279744 was reported to be associated with a nine-fold increase in the risk of death [28]. Moreover, the simultaneous presence of wildtype allele of TP53 rs1042522 and the variant allele of MDM2 rs2279744 may influence the risk of therapy-related myeloid neoplasms [29]. MDM2 rs3730485 and MDM4 rs4245739 variants were studied in different types of cancer, together or in combination with one or with the other two mentioned variants, but from our knowledge, AML patients were not investigated.…”

Section: Introductionmentioning

confidence: 99%

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Association Analysis of TP53 rs1042522, MDM2 rs2279744, rs3730485, MDM4 rs4245739 Variants and Acute Myeloid Leukemia Susceptibility, Risk Stratification Scores, and Clinical Features: An Exploratory Study

Tripon

Iancu

Crauciuc

et al. 2020

JCM

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This study aimed to explore the associations between the TP53 rs1042522 (TP53 Arg72Pro), MDM2 rs2279744 (MDM2 309T>G), rs3730485 (MDM2 del1518), MDM4 rs4245739 (MDM4 34091 C>A) variants and odds of developing acute myeloid leukemia (AML) in a cohort of 809 adult subjects, consisting of 406 healthy controls and 403 AML patients. Model-based multifactor dimensionality reduction (MB-MDR) framework was used to identify the interactions of the mentioned variants and their association with AML risk. Associations of the mentioned variants with clinical features of AML, somatic mutations, and response to treatment were also evaluated. Significant associations between TP53 rs1042522 and MDM4 rs4245739 variants and AML susceptibility were noticed. MB-MDR and logistic regression analysis revealed an interaction between MDM2 rs2279744 and TP53 rs1042522, between MDM4 rs4245739 and MDM2 rs3730485, as well as significant associations with AML susceptibility. Several associations between the mentioned variants and clinical features of AML and somatic mutations were also noticed. Individually, the variant genotypes of TP53 rs1042522 and MDM4 rs4245739 were associated with AML susceptibility, but their interaction with MDM2 rs2279744 and rs3730485 modulated the risk for AML. The variant genotypes of TP53 rs1042522 were associated with adverse molecular and cytogenetic risk and also with NPM1 mutations.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association Analysis of TP53 rs1042522, MDM2 rs2279744, rs3730485, MDM4 rs4245739 Variants and Acute Myeloid Leukemia Susceptibility, Risk Stratification Scores, and Clinical Features: An Exploratory Study

Tripon

Iancu

Crauciuc

et al. 2020

JCM

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“…Further research in different ethnicities is required to confirm the involvement of these markers in VFL, as all studies included in this systematic review were performed in China. Although the evaluated genetic markers are present in other populations such as from Austria, United Kingdom, America, Turkey, India, Finland, France, Poland, Pakistan, Egypt, Tunisia, Thailand, Iran Spain, Brazil, and Mexico ( 28 , 50 , 60 - 74 ), to the best of our knowledge, there are no published studies on the involvement of genetic polymorphisms in patients with VFL from these countries.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms and protein levels in vocal fold leukoplakia: a systematic review

Campello

Lima-Silva

Lima

et al. 2022

Braz J Med Biol Res

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Vocal fold leukoplakia (VFL) has a risk of malignant transformation. Therefore, patients can have symptoms such as dysphonia, vocal strain, difficulty breathing, and dysphagia. Additionally, there is a genetic predisposition that can be associated with genetic polymorphisms. We aimed to evaluate the influence of genetic polymorphisms and protein levels in the etiology of VFL. Our study followed the PRISMA checklist and was registered on PROSPERO database. The questions were: “Are genetic polymorphisms involved in the etiology of VFL? Are protein levels altered in patients with VFL?”. Eligibility criteria were case control studies that compared the presence of polymorphisms or/and protein levels of subjects diagnosed with VFL and healthy controls. Of the 905 articles retrieved, five articles with a total of 1038 participants were included in this study. The C allele of the single nucleotide polymorphisms (SNP)-819 T/C IL-10 , A allele of the SNP -592 A/C IL-10 , CT genotype of the SNP rs11886868 C/T BCL11A , GG genotype of the SNP rs4671393 A/G BCL11A , LL genotype, and L allele of (GT)n repeat polymorphisms of the HO-1 were risk factors for VFL development. Nevertheless, there was a lack of association between VFL and the -1082 A/G IL-10 , rs14024 CK-1 , and -309 T/G Mdm2 SNPs. The concentrations of the MDM2, BCL11A, and HO-1 proteins were modified, while IL-10 levels were normally expressed in these subjects. In conclusion, most markers evaluated in this review could be potential indicators to develop effective therapies, avoiding a malignant transformation of the lesion.

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“…Colcemid was added 24 h before the extraction. The following steps until scoring the SCE values were the same used by Cabezas et al (2019).…”

Section: Methodsmentioning

confidence: 99%

Differential biological effect of low doses of ionizing radiation depending on the radiosensitivity in a cell line model

Palma-Rojo,

Barquinero,

Pérez-Alija

et al. 2024

Preprint

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Purpose Exposure to low doses (LD) of ionizing radiation (IR), such as the ones employed in computed tomography (CT) examination, can be associated with cancer risk. However, not all individuals respond the same to IR, and cancer development could depend on the individual radiosensitivity. Notably, inter-individual differences in the response to IR have been very well studied for high and medium doses, but not for LD. In the present study, we wanted to evaluate the differences in the response to a CT-scan radiation dose of 20 mGy in two lymphoblastoid cell lines with different radiosensitivity. Materials and Methods Several parameters were studied: gene expression, DNA damage, and its repair (by analyzing gamma-H2AX foci, chromosome breaks, and sister chromatid exchange), as well as cell viability, proliferation, and death. Results After 20 mGy of IR, the radiosensitive (RS) cell line showed an increase in DNA damage, and higher cell proliferation and apoptosis, whereas the radioresistant (RR) cell line was insensitive to this LD. Interestingly, gene expression analysis showed a higher expression of an antioxidant gene in the RR cell line, which could be used by the cells as a protective mechanism. After a dose of 500 mGy, both cell lines were affected by IR but with significant differences. The RS cells presented an increase in DNA damage and apoptosis, but a decrease in cell proliferation and cell viability, as well as less antioxidant response. Conclusions A differential biological effect was observed between two cell lines with different radiosensitivity, and these differences are especially interesting after a CT scan dose. If this is confirmed by further studies, one could think that individuals with radiosensitivity-related genetic variants may be more vulnerable to long-term effects of IR, potentially increasing cancer risk after LD exposure.

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

Cited by 6 publications

References 46 publications

Association Analysis of TP53 rs1042522, MDM2 rs2279744, rs3730485, MDM4 rs4245739 Variants and Acute Myeloid Leukemia Susceptibility, Risk Stratification Scores, and Clinical Features: An Exploratory Study

Association Analysis of TP53 rs1042522, MDM2 rs2279744, rs3730485, MDM4 rs4245739 Variants and Acute Myeloid Leukemia Susceptibility, Risk Stratification Scores, and Clinical Features: An Exploratory Study

Genetic polymorphisms and protein levels in vocal fold leukoplakia: a systematic review

Differential biological effect of low doses of ionizing radiation depending on the radiosensitivity in a cell line model

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