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

ABSTRACT: 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.

SUBMITTER: Yin L

PROVIDER: S-EPMC7049506 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Yin Lele L Shen Guo G Zhu Bin B

Thoracic cancer 20200122 3

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 31970867

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Project description:Purpose: To investigate the role of the mouse double minute 2 (MDM2) gene single-nucleotide polymorphism (SNP) T309G in the development of epimacular membranes (EMMs) by analyzing the genotype distribution and consistency of the polymorphism in paired membrane-blood samples. Methods: This was a cross-sectional genetic association study of patients with proliferative vitreoretinopathy (PVR) or EMMs. PVR membranes (PVRMs), internal limiting membranes (ILMs) (PVR-ILMs) and blood samples (PVR-blood) from patients with PVR, and EMMs, EMM-ILMs and EMM-blood from patients with EMMs were collected. The genotype of all samples was determined by Sanger sequencing. Sex composition, mean age, the genotype distribution of MDM2 T309G, the allelic frequency of the MDM2 SNP309 G allele (% G) and the somatic mutation rate at the MDM2 T309G locus (% M) were analyzed and compared. The PVR and healthy Chinese donor groups were used as controls for different comparisons. Results: The EMM group of 62 patients was older than the PVR group of 61 patients by an average of 8.87 years (p < 0.0001), but the two groups were statistically similar in the sex composition (p = 0.1754). Importantly, G allele carriers were at a higher risk of developing EMMs than non-G allele carriers (p = 0.0479; OR = 2.047). Moreover, EMM-blood exhibited a significantly higher % G than blood samples from healthy Chinese donors (EMM-blood: 56.78%, donors: 45.61%; p = 0.0256; OR = 1.567). Regarding membrane-blood consistency, % M was significantly different between PVRMs and EMMs (PVRMs: 2.63%, EMMs: 21.57%; p = 0.0097; OR = 10.18) but not between different types of ILMs (PVR-ILMs: 18.18%, EMM-ILMs: 29.17%; p = 0.6855). Furthermore, EMMs (p = 0.0053; OR = 8.250) and EMM-ILMs (p = 0.0233; OR = 14.40) from patients with preoperative macular holes were more predisposed toward somatic mutations at the MDM2 T309G locus than those from patients without preoperative macular holes. Conclusions: MDM2 T309G is associated with the development of EMMs. Herein, the MDM2 SNP309 G allele is first reported as an associated factor of EMMs in a Chinese population. In addition, EMMs and ILMs are genetically unstable at the MDM2 T309G locus, especially when complicated with preoperative macular holes.

Project description:BackgroundThe tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP) at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory.MethodsTo investigate whether currently published epidemiological studies can clarify the potential interaction between MDM2 SNP309 and the functional genetic variant in p53 codon72 (Arg72Pro) and p53 mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls.ResultsThe data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17). We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively). In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively). However, no association was seen between MDM2 SNP309 and tumor susceptibility in the stratified analysis by p53 mutation status (GG vs TT: OR = 1.17, 95% CI = 0.75-1.82 and TG vs TT: OR = 1.09, 95% CI = 0.89-1.34 for positive p53 mutation status; GG vs TT: OR = 0.95, 95% CI = 0.72-1.25 and TG vs TT: OR = 1.06, 95% CI = 0.85-1.30 for negative p53 mutation status).ConclusionsThe analyses indicate that MDM2 SNP309 serves as a tumor susceptibility marker, and that there is an association between MDM2 SNP309 and p53 Arg72Pro regarding tumor susceptibility. Further studies that take into consideration environmental stresses and functional genetic variants in the p53-MDM2-related genes are warranted.

Project description:BackgroundGynecological malignant tumor is a serious threat to women's health, cervical cancer, endometrial cancer and ovarian cancer are the most common. The eponymous protein encoded by the XRCC1 (X-ray repair cross complementation 1) gene is an important functional protein in the process of single-stranded DNA damage. Non-synonymous mutations of XRCC1 gene cause amino acid sequence changes that affect protein function and DNA repair ability, and may affect the interaction with other DNA repair proteins, leading to increased risk of tumor development. Many studies have assessed the association between XRCC1 gene polymorphism and the risk of cancer in the female reproductive system, but the results have been inconclusive. In this study, the relationship between XRCC1 Arg399Gln, Arg194Trp, Arg280His single nucleotide polymorphisms and susceptibility to gynecological malignancies was further explored by meta-analysis.MethodsEnglish database: Pubmed, Medline, Excerpta Medica Database, Cochrance, etc; Chinese database: China national knowledge infrastructure, Wanfang Database, etc. STATA14 was used for statistical analysis, such as odd ratio (OR) value, subgroup analysis, heterogeneity test, sensitivity analysis, and publication bias.ResultsIn gynecologic cancers, the allele frequency difference of Arg399Gln case control group was statistically significant (GvsA: P = .007). There was no significant difference in allele frequency in the Arg194Trp and Arg280His case control groups (P = .065, 0.198). In different gene models, Arg399Gln was significantly correlated with gynecologic cancers susceptibility (GGvs AA: OR 0.91; 95% confidence interval [CI], 0.85 0.98); Arg194Trp was significantly correlated with gynecologic cancers susceptibility (CCvs TT: OR 0.94; 95% CI 0.88,1.00; CCvs CT: OR 0.97; 95% CI 0.90, 1.05); Arg280His was significantly correlated with gynecologic cancers susceptibility (GGvs AA: OR 0.98; 95% CI 0.94, 1.02; GGvs GA: OR 1.00;95% CI 0.97, 1.04). In the subgroup analysis, Arg399Gln and Arg194Trp were significantly correlated with gynecologic cancers susceptibility in the Asian race (P = .000, 0.049). In the analysis of different cancer subgroups, Arg399Gln and cervical cancer susceptibility were statistically significant (P = .039). Arg194Trp and endometrial cancer susceptibility were statistically significant (P = .033, 0.001).ConclusionsXRCC1 Arg399Gln, Arg194Trp, Arg280His single nucleotide polymorphisms were associated with gynecologic cancer susceptibility. Arg399Gln genotype was statistically significant in relation to cervical cancer susceptibility. Arg194Trp genotype was statistically significant in relation to endometrial cancer susceptibility.

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

Publications

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

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