Dataset Information

The Role of p16 and MDM2 Gene Polymorphisms in Prolactinoma: MDM2 Gene Polymorphisms May Be Associated with Tumor Shrinkage.

ABSTRACT: Prolactinomas are thought to arise from clonal expansion of a single mutated cell which is subjected to growth stimuli of several permissive factors, although the pathogenetic mechanisms underlying tumorigenesis remain unclear. The present study aimed to investigate the role of p16 (540C?G and 580C?T) and mouse double minute 2 (MDM2) (SNP309T?G) gene polymorphisms in tumorigenesis and characteristics of prolactinoma.A total of 74 patients with prolactinoma and 100 age- and gender-matched healthy individuals were enrolled in the study. Serum prolactin levels were measured by enzyme-linked immunosorbent assay (ELISA). p16 and MDM2 polymorphisms were determined by polymerase chain reaction-restriction fragment polymorphism and agarose gel electrophoresis.p16 540C?G genotype distribution was found to be: CC: 66.2%, CG: 28.4%, GG: 5.4%; p16 580C?T genotype distribution was found to be: CC: 82.4%, CT: 17.6%, TT: 0% and MDM2 genotype distribution was found to be: TT: 31.1%, TG: 47.3%, GG: 21.6% in patients with prolactinoma. Tumor diameter before treatment was correlated with prolactin levels before treatment and percentage of prolactin decrease with treatment (r=0.719, p<0.001, p=0.034 r=0.256, respectively). The number of patients with tumor size decrease of more than 50% in those with homozygous genotype (TT+GG) of MDM2 SNP309T?G was significantly higher than in heterozygous genotype (TG) carriers (odds ratio(OR)=0.18, 95% confidence interval(CI)=0.06-0.58; p=0.003).This study showed that p16 and MDM2 polymorphisms do not play a decisive role in tumorigenesis, but some genotypes of these polymorphisms might be associated with follow-up characteristics of prolactinoma.

SUBMITTER: Turgut S

PROVIDER: S-EPMC5461445 | biostudies-literature | 2017 May-Jun

REPOSITORIES: biostudies-literature

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The Role of <i>p16</i> and <i>MDM2</i> Gene Polymorphisms in Prolactinoma: <i>MDM2</i> Gene Polymorphisms May Be Associated with Tumor Shrinkage.

Turgut Seda S Ilhan Muzaffer M Turan Saime S Karaman Ozcan O Yaylim Ilhan I Kucukhuseyin Ozlem O Tasan Ertugrul E

In vivo (Athens, Greece) 20170501 3

<h4>Aim</h4>Prolactinomas are thought to arise from clonal expansion of a single mutated cell which is subjected to growth stimuli of several permissive factors, although the pathogenetic mechanisms underlying tumorigenesis remain unclear. The present study aimed to investigate the role of p16 (540C→G and 580C→T) and mouse double minute 2 (MDM2) (SNP309T→G) gene polymorphisms in tumorigenesis and characteristics of prolactinoma.<h4>Patients and methods</h4>A total of 74 patients with prolactinom ...[more]

PMID: 28438863

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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:BackgroundThe association between TP53 R72P and/or MDM2 SNP309 polymorphisms and hepatocellular carcinoma (HCC) risk has been widely reported, but results were inconsistent. To clarify the effects of these polymorphisms on HCC risk, an updated meta-analysis of all available studies was conducted.MethodsEligible articles were identified by search of databases including PubMed, Cochrane Library, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to July 2013. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity.ResultsFinally, a total of 10 studies including 2,243 cases and 3,615 controls were available for MDM2 SNP309 polymorphism and 14 studies containing 4,855 cases and 6,630 controls were included for TP53 R72P polymorphism. With respect to MDM2 SNP309 polymorphism, significantly increased HCC risk was found in the overall population. In subgroup analysis by ethnicity and hepatitis virus infection status, significantly increased HCC risk was found in Asians, Caucasians, Africans, and HCV positive patients. With respect to TP53 R72P polymorphism, no significant association with HCC risk was observed in the overall and subgroup analyses. In the MDM2 SNP309-TP53 R72P interaction analysis, we found that subjects with MDM2 309TT and TP53 Pro/Pro genotype, MDM2 309 TG and TP53 Arg/Pro genotype, and MDM2 309 GG and TP53 Pro/Pro genotype were associated with significantly increased risk of developing HCC as compared with the reference MDM2 309TT and TP53 Arg/Arg genotype.ConclusionsWe concluded that MDM2 SNP309 polymorphism may play an important role in the carcinogenesis of HCC. In addition, our findings further suggest that the combination of MDM2 SNP 309 and TP53 Arg72Pro genotypes confers higher risk to develop HCC. Further large and well-designed studies are needed to confirm this association.

Dataset Information

The Role of p16 and MDM2 Gene Polymorphisms in Prolactinoma: MDM2 Gene Polymorphisms May Be Associated with Tumor Shrinkage.

Publications

The Role of <i>p16</i> and <i>MDM2</i> Gene Polymorphisms in Prolactinoma: <i>MDM2</i> Gene Polymorphisms May Be Associated with Tumor Shrinkage.

Similar Datasets

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