Polymorphisms at p53, p73, and MDM2 loci modulate the risk of tobacco associated leukoplakia and oral cancer

Misra, Chaitali; Majumder, Mousumi; Bajaj, Swati; Ghosh, Saurabh; Roy, Bidyut; Roychoudhury, Susanta

doi:10.1002/mc.20523

Cited by 56 publications

(49 citation statements)

References 49 publications

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“…Five independent studies investigating the genetic effects of MDM2 SNP309T>G on OSCC risk (9-13) were included in this meta-analysis. Among these, 1 study demonstrated that MDM2 SNP309T>G was associated with a reduced risk of OSCC (13), while the remaining 4 studies provided no evidence of an association between this SNP and OSCC risk (9)(10)(11)(12). A meta-analysis of the 5 studies, including 1,369 cases and 2,167 controls, was performed to investigate the overall effects of MDM2 SNP309 on OSCC risk.…”

Section: Discussionmentioning

confidence: 99%

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Association of MDM2 promoter T309G polymorphism with oral cancer risk: A meta-analysis of 3,536 subjects

Yang

Zhu

et al. 2016

Molecular and Clinical Oncology

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Abstract. The mouse double minute 2 (MDM2) gene is an important regulator of the p53 suppressor gene. To date, evidence concerning the association of the MDM2 single nucleotide polymorphism (SNP) 309T>G (rs2279744) with the risk of developing oral squamous cell carcinoma (OSCC) remains controversial. Therefore, a meta-analysis of all the eligible studies was performed, in order to derive a more precise estimation of this association. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the degree of association in 5 previous studies, including a total of 1,369 OSCC cases and 2,167 controls. The overall analysis revealed a significant association between MDM2 SNP309 and OSCC risk in the heterozygote (TG vs. TT: OR=0.81; 95% CI: 0.68-0.96; P=0.02) and dominant models (TG+GG vs. TT: OR=0.82; 95% CI: 0.69-0.97; P=0.02). The subgroup analysis based on the source of the controls revealed a significant association between population-based controls and the heterozygote model (TG vs. TT: OR=0.75; 95% CI: 0.62-0.91; P=0.004), dominant model (TG+GG vs. TT: OR=0.76; 95% CI: 0.63-0.91; P=0.003) and allele comparison (G vs. T: OR=0.89; 95% CI: 0.79-0.99; P=0.04). Importantly, no evidence of publication bias or obvious heterogeneity were observed in the meta-analysis. The results of the present study demonstrated a decreased risk of developing OSCC for the MDM2 SNP309 group, suggesting MDM2 SNP309 may be a protection-associated genetic variation for OSCC. Additional well-designed studies, with larger sample sizes, are required to further elucidate this association. IntroductionOral cancer is one of the most common cancers worldwide, with an unclear pathogenesis; the oral squamous cell carcinoma (OSCC) subtype accounts for >90% of all oral cancers (1). While increasing evidence suggests that environmental factors, as well as chemical carcinogens (including tobacco and alcohol) are likely etiological factors that contribute to the development of OSCC, only a small minority of individuals exposed to these carcinogens will subsequently develop head and neck SCC (2,3). Oral carcinogenesis is widely recognized as a stepwise process, and the involvement of genetic alterations and host polymorphisms may be important to its development (4). The identification of a predictive model of risk polymorphisms may facilitate early diagnosis and the understanding of disease progression in a subset of cancer patients (4).The human mouse double minute 2 (MDM2) gene is an important negative regulator of the p53 suppressor gene, promoting the degradation of p53 through its E3 ubiquitin ligase activity (5). A functional single-nucleotide polymorphism (SNP), rs2279744, is located at nucleotide 309 in the first intron of the MDM2 promoter region, consisting of a change from T to G. This mutation has been named SNP309 (6). SNP 309T>G is known to enhance the binding affinity of the transcriptional activator SP1, contributing to increased expression of MDM2 and subsequent attenuation of the p53 tumor suppressor pathway (6). MDM2 SNP3...

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Section: Discussionmentioning

confidence: 99%

“…To date, numerous previous studies have investigated the association between MDM2 SNP309 and OSCC risk (9)(10)(11)(12)(13)(14)(15). However, the results remain inconsistent and ambiguous, partly due to the relatively small sample sizes of the independent studies and sampling effects.…”

Section: Introductionmentioning

confidence: 99%

Association of MDM2 promoter T309G polymorphism with oral cancer risk: A meta-analysis of 3,536 subjects

Yang

Zhu

et al. 2016

Molecular and Clinical Oncology

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“…In addition, one recent meta-analysis also detected no evidence of a significant association between the TP53 Arg72Pro polymorphism and risk of oral cancer (Zhuo et al, 2009b), and another meta-analysis observed a significant association of the TP53 Arg72Pro polymorphism with nasopharyngeal cancer susceptibility (Zhuo et al, 2009a), which are all consistent with our results. Nevertheless, three more eligible articles related to oral cancer (Tandle et al, 2001;Kietthubthew et al, 2003;Misra et al, 2009) and one more eligible article related to nasopharyngeal cancer (Golovleva et al, 1997) were included in our meta-analysis that were not included in the two previous meta-analyses.…”

Section: Discussionmentioning

confidence: 99%

“…Shen et al (2002) analyzed oral, pharyngeal, and laryngeal cancer specifically, whereas Ji et al (2008) and Chen et al (2008) studied oropharyngeal cancer as well as oral cancer. Overall, a total of 27 studies consisting of 3966 HNCs cases and 4387 controls were included in our meta-analysis (Yung et al, 1997;Golovleva et al, 1997;McWilliams et al, 2000;Hamel et al, 2000;Summersgill et al, 2000;Tandle et al, 2001;Sourvinos et al, 2001;Nagpal et al, 2002;Shen et al, 2002;Tsai et al, 2002;Tiwawech et al, 2003;Kietthubthew et al, 2003;Katiyar et al, 2003;Scheckenbach et al, 2004;Cortezzi et al, 2004;Hsieh et al, 2005;Sousa et al, 2006;Twu et al, 2006;Hadhri-Guiga et al, 2007;Perrone et al, 2007;Kuroda et al, 2007;Ji et al, 2008;Chen et al, 2007Chen et al, , 2008Lin et al, 2008;Tu et al, 2008;Misra et al, 2009) (Table 2). The genotype distribution of the TP53 Arg72Pro polymorphism is summarized in Table 3.…”

Section: Literature Search Screening and Data Collectionmentioning

confidence: 99%

Meta-analysis of associations between the TP53 Arg72Pro polymorphism with risk of head and neck carcinomas based on case-control studies

et al. 2014

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ABSTRACT. Genetic factors have been shown to play a role in the development of head and neck cancers (HNCs). However, studies investigating the association between the TP53 Arg72Pro polymorphism and HNCs susceptibility have yielded conflicting results. Hence, we performed a meta-analysis of all eligible studies (up to January 1, 2012) to derive a more precise estimation of this association in order to increase understanding of the possible risk factors of HNCs. Twenty-seven casecontrol studies involving 3966 cases and 4387 controls were included in our analysis. Overall, no evidence of association was observed between the TP53 Arg72Pro single nucleotide polymorphism (SNP) and the risk of effects across different subtypes of HNCs. For example, there was a lack of association of this polymorphism with oral cavity cancer, whereas a significant association with nasopharyngeal cancer was observed. Results of this meta-analysis suggest that the TP53 Arg72Pro polymorphism might have different effects on the risk of various subtypes of HNCs.

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“…Of these regulators, the murine double minute clone 2 (MDM2) proto-oncogene, an important negative regulator of the p53 gene, has become a point of interest (8). MDM2 is a major regulator of p53 function.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the association between the MDM2 T309G polymorphism and gastric cancer

et al. 2017

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Abstract. Murine double minute clone 2 oncoprotein (MDM2) is a key component in the regulation of the tumour suppressor p53. The association between the MDM2 polymorphism and gastric cancer (GC) has been investigated in Turkish population. In the present case-control study, the aim was to investigate the association between genetic polymorphisms of the MDM2 gene (a major regulator of p53 function) and primary GC risk in a Turkish population. The polymorphism, T309G (rs2279744) in the MDM2 gene was determined in patients with GC (n=65) and in healthy control subjects (n=67) using the polymerase chain reaction-restriction fragment length polymorphism method. The findings were evaluated using logistic regression and χ 2 tests. No statistically significant differences were observed between the control subjects and patients with GC regarding smoking status. A comparison between GC cases and control subjects indicated a statistically significant difference for family history of cancer [odds ratio (OR)=0.17; 95% confidence interval (CI), 0.05-0.56; χ 2 =0.19; P=0.01]. A significant difference was identified in the GG genotype distribution between GC patients and control subjects (OR=4.58; 95% CI, 1.18-17.79; P=0.022). Thus, the results of the present study indicate that the MDM2 gene T309G intron (GG) genotype may be an important risk factor for GC development in the Turkish population.

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Polymorphisms at p53, p73, and MDM2 loci modulate the risk of tobacco associated leukoplakia and oral cancer

Cited by 56 publications

References 49 publications

Association of MDM2 promoter T309G polymorphism with oral cancer risk: A meta-analysis of 3,536 subjects

Association of MDM2 promoter T309G polymorphism with oral cancer risk: A meta-analysis of 3,536 subjects

Meta-analysis of associations between the TP53 Arg72Pro polymorphism with risk of head and neck carcinomas based on case-control studies

Investigation of the association between the MDM2 T309G polymorphism and gastric cancer

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