Roles of CDKN1A gene polymorphisms (rs1801270 and rs1059234) in the development of cervical neoplasia

Vargas-Torres, Sandra; Portari, Elyzabeth Avvad; Silva, Amanda Lima; Klumb, Evandro Mendes; Guillobel, Heloísa Carneiro da Rocha; Camargo, Maria José de; Santos-Rebouças, Cíntia Barros; Russomano, Fábio Bastos; Macedo, Jacyara Maria Brito

doi:10.1007/s13277-016-4850-3

Cited by 16 publications

(15 citation statements)

References 42 publications

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“…In Chinese and in non-Asian women, the missense variant c.93C > A located in codon 31 was associated with protective effects against cervical cancer [83,84]. In the Brazilian population, c.93C > A and c.*20C > T (located in 3 0 UTR) variants of CDKN1A were also associated with protection against cervical cancer [85]. CDKN1A was found to be hypermethylated in less than 10% of cervical cancer samples [31].…”

Section: Cell Cycle Regulation and Dna Repairmentioning

confidence: 94%

Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Cardoso

Castelletti

Lima-Filho

et al. 2017

Mutation Research/Reviews in Mutation Research

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Cervical cancer is primarily caused by Human papillomavirus (HPV) infection, but other factors such as smoking habits, co-infections and genetic background, can also contribute to its development. Although this cancer is avoidable, it is the fourth most frequent type of cancer in females worldwide and can only be treated with chemotherapy and radical surgery. There is a need for biomarkers that will enable early diagnosis and targeted therapy for this type of cancer. Therefore, a systems biology pipeline was applied in order to identify potential biomarkers for cervical cancer, which show significant reports in three molecular aspects: DNA sequence variants, DNA methylation pattern and alterations in mRNA/protein expression levels. CDH1, CDKN2A, RB1 and TP53 genes were selected as putative biomarkers, being involved in metastasis, cell cycle regulation and tumour suppression. Other ten genes (CDH13, FHIT, PTEN, MLH1, TP73, CDKN1A, CACNA2D2, TERT, WIF1, APC) seemed to play a role in cervical cancer, but the lack of studies prevented their inclusion as possible biomarkers. Our results highlight the importance of these genes. However, further studies should be performed to elucidate the impact of DNA sequence variants and/or epigenetic deregulation and altered expression of these genes in cervical carcinogenesis and their potential as biomarkers for cervical cancer diagnosis and prognosis.

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Section: Cell Cycle Regulation and Dna Repairmentioning

confidence: 94%

Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Cardoso

Castelletti

Lima-Filho

et al. 2017

Mutation Research/Reviews in Mutation Research

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“…p21 is the major downstream effector of p53, which can act as a mediator between p53, DNA damage and repair and cell-cycle inhibition. 33 Due to the complex function of p21, p21 exhibits both tumor suppressor and oncogenic attributes. 34 Several studies have been reported the effects of P21 polymorphisms on the function of its protein and may contribute to cancer susceptibility.…”

Section: Discussionmentioning

confidence: 99%

“…p21 is the major downstream effector of p53, which can act as a mediator between p53, DNA damage and repair and cell‐cycle inhibition . Due to the complex function of p21, p21 exhibits both tumor suppressor and oncogenic attributes .…”

Section: Discussionmentioning

confidence: 99%

The effect of TP53 and P21 gene polymorphisms on papillary thyroid carcinoma susceptibility and clinical/pathological features

et al. 2020

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Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Genetic polymorphisms of the TP53 and P21 genes are the candidate variants in various cancers development. This study investigated whether the polymorphisms in TP53 (rs1042522) and P21 (rs1059234 and rs1801270) affect the risk of PTC and whether such the genotype of these polymorphisms is associated with pathological and clinical characteristics of PTC. A case–control study was conducted with 286 Iranian people, including 131 PTC cases and 155 healthy controls. The genetic polymorphisms were investigated by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Our results suggested that TP53‐rs1042522 CC genotype was significantly associated with protection against PTC, in the dominant, recessive and allelic models (OR = 0.4, 95%CI: 0.2–0.8, P = .008; OR = 0.5, 95%CI: 0.3–0.9, P = .01; OR = 0.6, 95%CI: 0.4–0.8, P = .002, respectively). The rs1042522 was associated with PTC patients with tumor size greater than 1 cm in dominant and recessive models (OR = 0.2, 95%CI = 0.04–0.9, P = .04 and OR = 0.3, 95%CI = 0.1–0.7, P = .009, respectively) and was associated with vascular invasion in dominant model (OR = 0.3, 95%CI = 0.1–0.7, P = .01). No correlation was identified between P21 rs1059234 and rs1801270 polymorphisms and risk of PTC and pathological and clinical characteristics of PTC. Genetic variations in rs1042522 might alter the PTC risk, which could affect tumor size and cause lower incidence of vascular invasion in PTC cases. This was the first report suggesting that no correlation was found between P21 rs1059234 and rs1801270 polymorphisms and PTC risk. Thus, more studies with a larger population size and different ethnic groups and functional assays are needed to confirm our results.

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“…Several studies show an association between CDKN1A -SNPs and cancer and patient survival prognostics (e.g. Cazier et al 2014 ; Kang et al 2015 ; Vargas-Torres et al 2016 ). A recent study of Price et al ( 2015 ) suggests that CDKN1A regulates Langerhans cell and could influence the response of cutaneous tumours to radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Combining CDKN1A gene expression and genome-wide SNPs in a twin cohort to gain insight into the heritability of individual radiosensitivity

Żyła

Kabacik

O’Brien

et al. 2019

Funct Integr Genomics

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Individual variability in response to radiation exposure is recognised and has often been reported as important in treatment planning. Despite many efforts to identify biomarkers allowing the identification of radiation sensitive patients, it is not yet possible to distinguish them with certainty before the beginning of the radiotherapy treatment. A comprehensive analysis of genome-wide single-nucleotide polymorphisms (SNPs) and a transcriptional response to ionising radiation exposure in twins have the potential to identify such an individual. In the present work, we investigated SNP profile and CDKN1A gene expression in blood T lymphocytes from 130 healthy Caucasians with a complex level of individual kinship (unrelated, mono- or dizygotic twins). It was found that genetic variation accounts for 66% (95% CI 37–82%) of CDKN1A transcriptional response to radiation exposure. We developed a novel integrative multi-kinship strategy allowing investigating the role of genome-wide polymorphisms in transcriptomic radiation response, and it revealed that rs205543 ( ETV6 gene), rs2287505 and rs1263612 ( KLF7 gene) are significantly associated with CDKN1A expression level. The functional analysis revealed that rs6974232 ( RPA3 gene), involved in mismatch repair ( p value = 9.68e−04) as well as in RNA repair ( p value = 1.4e−03) might have an important role in that process. Two missense polymorphisms with possible deleterious effect in humans were identified: rs1133833 ( AKIP1 gene) and rs17362588 ( CCDC141 gene). In summary, the data presented here support the validity of this novel integrative data analysis strategy to provide insights into the identification of SNPs potentially influencing radiation sensitivity. Further investigations in radiation response research at the genomic level should be therefore continued to confirm these findings. Electronic supplementary material The online version of this article (10.1007/s10142-019-00658-3) contains supplementary material, which is available to authorized users.

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Roles of CDKN1A gene polymorphisms (rs1801270 and rs1059234) in the development of cervical neoplasia

Cited by 16 publications

References 42 publications

Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

The effect of TP53 and P21 gene polymorphisms on papillary thyroid carcinoma susceptibility and clinical/pathological features

Combining CDKN1A gene expression and genome-wide SNPs in a twin cohort to gain insight into the heritability of individual radiosensitivity

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