Impact of<i>MDM2, TP53</i>and<i>P14ARF</i>Polymorphisms on Endometrial Cancer Risk and Onset

Wujcicka, Wioletta; Zając, Agnieszka; Stachowiak, Grzegorz

doi:10.21873/invivo.11559

Cited by 5 publications

(9 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies on correlations between p14ARF and endometrial cancer have, so far, been rather not numerous, while p14ARF is a component of the p53 pathway (p14ARF/MDM2/p53), essential for the development and progression of various in vivo 34: 943-951 (2020) human neoplasms, including EC (4,5,22). Certain modulations in EC cells kinetics, possible via alterations in this pathway, [p14ARF/p53/p21(WAF1)], may result from a correlation between Sox9 and NF-ĸB signalling mechanisms, as well as from the Akt status (26).…”

Section: Discussionmentioning

confidence: 99%

“…Taking into account our previous studies, we demonstrated that the SNP309 polymorphism of the MDM2 gene is strongly associated with EC (both the GG genotype and the G allele), while the TP53 codon 72 polymorphism has been of a prognostic value and useful for the prophylaxis from EC (the Arg/Arg homozygote has been linked with an increased, while the Pro/Arg heterozygote and the Pro allele -with a decreased EC risk) (35)(36)(37). Moreover, the research about the joint effect of MDM2 SNP309, TP53 rs1042522, and the three currently described P14ARF polymorphisms on the onset of EC in postmenopausal women, concluded that MDM2 SNP309 plays a role in this cancer (22). The multiple-SNP combinations G-Arg-C-T-G for MDM2, TP53, and the three P14ARF polymorphisms, increased EC risk, while the T-Arg-C-T-G variants decreased risk for disease (22).…”

Section: Discussionmentioning

confidence: 99%

“…The primer sequences and conditions of the PCR assays are presented in Table II. The external primers were designed, using the PerlPrimer v1.1.21 software, and the internal primers were obtained from the literature (15,19,(22)(23)(24). Nested PCR products were resolved on 1% agarose gels, stained with ethidium bromide, and then digested overnight with HaeIII (EURx, Gdansk, Poland), and MvaI (Thermo Fisher Scientific, Waltham, MA, USA) endonucleases to determine genotypes of rs3088440 and rs3731217, as well as of rs3731245 polymorphisms, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…It is noteworthy that TGA/CAG diplotypes and TGA/TAG variants for rs3731217, rs3731245, and rs3088440 SNPs, have been proposed to possibly be associated with a decreased and an increased risk of chronic benzene poisoning, respectively (21). Our previous study, performed in postmenopausal women with EC, has shown the joint effect of MDM2 SNP309, TP53 SNP rs1042522, as well as of the three polymorphisms of P14ARF in the occurrence of the cancer (22). Based on the reported changes in the protein levels of p14ARF tumour suppressor, involved in EC, as well as previous research on the functional role of the three SNPs, rs3088440, rs3731217 or rs3731245, residing within P14ARF gene, a further study seems to be justified and needed regarding the contribution of the presented polymorphisms to EC.…”

mentioning

confidence: 95%

See 3 more Smart Citations

Association of SNPs in CDKN2A (P14ARF) Tumour Suppressor Gene With Endometrial Cancer in Postmenopausal Women

Wujcicka¹,

Zając²,

Szyłło³

et al. 2020

In Vivo

Self Cite

View full text Add to dashboard Cite

Background/Aim: This research was aimed to evaluate the association between three selected single nucleotide polymorphisms (SNPs) within the CDKN2A (P14ARF) tumour suppressor gene and the incidence of endometrial cancer (EC) in postmenopausal women. Patients and Methods: The study included 194 postmenopausal women; 144 with EC and 50 noncancer controls. Genotypes in P14ARF rs3088440, rs3731217 and rs3731245 polymorphisms were assayed using PCR-RFLP and confirmed by sequencing. Results: Regarding the rs3088440 polymorphism, CT, and CT-TT genotypes, were more prevalent among EC patients than in controls (OR=5.55, p=0.023, OR=5.29, p=0.027; and OR=2.92, p=0.023, respectively). The T allele within rs3088440 was more prevalent in EC females than in controls (χ 2 =4.7, p=0.030). Considering rs3731217, TG and TG-GG genotypes were less prevalent among EC (OR=0.34, p=0.024 or p=0.023; and OR=0.38, p=0.035, respectively). Conclusion: Polymorphisms in the CDKN2A gene are associated with EC in postmenopausal women. Endometrial cancer (EC) is the fourth most common cancer among Polish women (after breast, colon, and lung cancer) responsible for 3% of cancer deaths in this population. Moreover, the incidence rate of this cancer has almost doubled in the last three decades, due to several factors, especially the increased average life expectancy of women. Hence, EC is predominantly observed in postmenopausal women in their sixth/seventh decade of life, with the highest incidence rate of 80/100,000 at the end of the seventh decade (1). P14ARF belongs to three tumour suppressor proteins, including p16INK4a and p15INK4b encoded by the CDKN2A gene, genetic changes of which may cause cellular proliferation and tumour growth (2, 3). It has been shown that p14ARF influenced the course of cell cycle by activating p53 and inhibiting MDM2 expression thus leading to cell cycle arrest in G 1 and G 2 /M phases (4, 5). Altered expression of p14ARF, either decreased or increased, has been found in various human tumours (5-8). Considering EC, tumor heterogeneity in CDKN2A protein expression between four different cores of primary tumours, has been reported as significantly more prevalent among samples with a higher stage of the disease (9). In another study, CDKN2A tumour suppressor gene was included in a panel of seven immunohistochemical markers [ER, CDKN2A (p16), TP53, VIM, PTEN, PGR, and IGF2BP3] to differentiate endometrioid carcinoma in FIGO grade 3 from serous carcinoma, based on immunohistochemical qualitative assays performed by tissue microarrays (10). Moreover, moderate immunohistochemical expression of p14 has been observed in endometrioid endometrial carcinoma, while total lack has been found in endometrial hyperplasias without atypia, at the 943 This article is freely accessible online.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 95%

See 2 more Smart Citations

Association of SNPs in CDKN2A (P14ARF) Tumour Suppressor Gene With Endometrial Cancer in Postmenopausal Women

Wujcicka¹,

Zając²,

Szyłło³

et al. 2020

In Vivo

Self Cite

View full text Add to dashboard Cite

show abstract

“…15 Overexpression or amplification of this gene has been detected in a variety of malignant carcinomas. 16,17 Studies have also determined that MDM2 309 T > G SNP were also correlated with an increased risk of solid tumors. Luan et al reported that MDM2 T309 G polymorphism may contribute to NSCLC susceptibility, especially in the Asian population and women.…”

Section: Discussionmentioning

confidence: 99%

Correlation between MDM2 T309G single nucleotide polymorphism and esophageal cancer susceptibility: An updated meta‐analysis

2020

View full text Add to dashboard Cite

Background The aim of this study was to investigate the correlation between MDM2 T309G single nucleotide polymorphism (SNP) and esophageal cancer susceptibility through pooling the open published data. Methods By systematic searching the databases of Medline, EMBASE, CBM and CNKI, the case‐control or cohort studies related to MDM2 T309G single nucleotide polymorphism and esophageal cancer risk were screened. Genetic phenotype data of T309G single nucleotide was extracted from the original included studies. The correlation between MDM2 T309G single nucleotide polymorphism and esophageal cancer susceptibility was demonstrated by the odds ratio (OR) and its corresponding 95% confidence interval (95% CI). Publication bias was investigated by Egger's line regression test and begg's funnel plot. Results After systematic searching of the relevant database, nine publications were finally included in the present study. The combined data demonstrated that the subjects with the G genotype had an increased risk of developing esophageal cancer in dominant (OR = 1.13, 95% CI: 1.00–1.27, P = 0.043), recessive (OR = 1.27, 95% CI: 1.12–1.45, P = 0.000) and homozygous (OR = 1.34, 95% CI:1.04–1.74, P = 0.024) genetic model through random or fixed data pooling method. Both begg's and Egger's line regression test indicated no significant publication bias. Conclusion Based on the present data, there was a significant correlation between MDM2 T309G single nucleotide polymorphism and esophageal cancer susceptibility. Individuals with G genotype may have an increased risk of developing esophageal cancer.

show abstract