Association of Arg72Pro of TP53 and T309G of MDM2 genes polymorphisms with non-small-cell lung cancer in Russians of the Moscow region

Логинов, В. И.; Atkarskaya, M. V.; Burdennyy, A. M.; Заварыкина, Т. М.; Kazubskaya, T. P.; Носиков, В. В.; Брага, Э. А.; Zhizhina, G. P.

doi:10.1134/s0026893314010099

Cited by 5 publications

(3 citation statements)

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“… 54 In addition, several reported studies have estimated the role of the interaction between the MDM2 / TP53 gene and several environmental factors, including smoking exposure, alcohol consumption, or human papillomavirus infections in SCC susceptibility. 13 , 29 , 38 , 40 , 41 For instance, rs2279744 and rs937283 of MDM2 might be associated with the occurrence of OSCC patients with HPV16 L1 seropositivity. 13 However, due to the lack of sufficient data, we failed to carry out a subgroup analysis based on these environmental factors.…”

Section: Discussionmentioning

confidence: 99%

Influence of <em>MDM2</em> polymorphisms on squamous cell carcinoma susceptibility: a meta-analysis

Yu¹,

Li²,

Zhang³

et al. 2016

OTT

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PurposeControversial associations between single-nucleotide polymorphisms (rs2279744, rs937283, rs3730485) of the MDM2 gene and the etiology of squamous cell carcinomas (SCCs) have been reported. This merits further comprehensive assessment.Materials and methodsWe systematically reviewed the available data and conducted an updated meta-analysis to evaluate the genetic effect of MDM2 polymorphisms in SCC susceptibility, using Stata/SE 12.0 software.ResultsAfter screening, 7,987 SCC cases and 12,954 controls from 26 eligible case–control studies were enrolled. Overall, compared with the control group, a significantly increased SCC risk was observed for the MDM2 rs2279744 polymorphism in the Asian population (test of association: odds ratio [OR] 1.12, P=0.027 for G vs T; OR 1.26, P=0.016 for GG vs TT; OR 1.25, P<0.001 for GG vs TT + TG; and OR 1.08, P=0.023 for carrier G vs T). In subgroup analysis by SCC type, a similarly increased esophageal SCC risk was detected (OR 1.19, P<0.001 for G vs T; OR 1.46, P<0.001 for GG vs TT; and OR 1.48, P=0.005 for GG vs TT + TG). Furthermore, MDM2–TP53 double mutation was statistically associated with increased SCC susceptibility overall (OR 1.52, P=0.001), especially in the Asian population (OR 1.49, P=0.022). However, no significant difference between the control and case groups was obtained for MDM2 rs937283 or rs3730485 under any genetic model (all P>0.05).ConclusionOur results highlight a positive association between the GG genotype of MDM2 rs2279744 polymorphism and an increased risk of esophageal SCC in the Asian population, which needs to be clarified by more large-scale studies.

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Section: Discussionmentioning

confidence: 99%

Influence of <em>MDM2</em> polymorphisms on squamous cell carcinoma susceptibility: a meta-analysis

Yu¹,

Li²,

Zhang³

et al. 2016

OTT

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“…TP53 polymorphisms have widely been studied in NSCLC, but the results are contradictory. Three studies reported a significantly increased risk (23)(24)(25), one (26) reported an insignificant risk increase, and three (9,17,27) (25), we, however, believe to be on the right track, since this TP53 variant has lower activity in apoptosis and its association with an increased NSCLC risk is plausible.…”

Section: Discussionmentioning

confidence: 87%

Association between the TP53 and CYP2E1*5B gene polymorphisms and non-small cell lung cancer

Ada

Bilgen

Volkan

et al. 2016

Archives of Industrial Hygiene and Toxicology

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Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Genetic polymorphisms in tumour suppressor genes and genes encoding xenobiotic metabolising enzymes alter the activity of their corresponding enzymes and are important individual susceptibility factors for NSCLC. Because of the lack of information in literature, the aim of our study was to investigate the role of the tumour suppressor gene TP53 (Arg72Pro) and the xenobiotic metabolising CYP2E1*5B gene polymorphisms on the risk of NSCLC development. The study population consisted of 172 patients and 172 controls (156 men and 16 women in each group). Genetic polymorphisms were determined with real-time polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). Multivariate analysis showed a significant association with NSCLC for the combination between the TP53 codon72 Arg/Pro and the Pro/Pro genotypes (OR 2.21, 95 % CI 1.39-3.51; p=0.001). We also analysed whether combinations of these gene variants with GSTM1, GSTT1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) gene polymorphisms were associated with the NSCLC risk. A significant increase in the risk was observed for the following combinations: TP53 codon72 variant with GSTM1 null (OR 2.22, 95 % CI 1.23-4.04; p=0.009), GSTT1 null (OR 2.98, 95 % CI 1.49-5.94; p=0.002), and GSTP1 (Ala114Val) variant genotypes (OR 3.38, p=0.002). Further studies with larger samples are needed to verify these findings. KEY WORDS: carcinogen metabolism; CYP2E1; genetic polymorphism; GST; NSCLCLung cancer is the most common cancer type in the world, which affects men in particular. It is also the leading cause of death among cancers (1). Histologically, about 80 % of lung cancers are non-small cell lung carcinomas (NSCLC). The inbuilt phase I and II biotransformation enzyme systems inactivate environmental carcinogens, especially those present in tobacco smoke, depending on the regulating polymorphisms. Epidemiological studies show that genetic differences and interactions among genetic variants might modify lung cancer susceptibility (2, 3). Therefore, it is important to identify individual genetic and acquired factors that modify lung cancer risk in order to develop preventive strategies based on this information. This is particularly true for identifying polymorphisms of tumour suppressor genes and xenobiotic metabolising enzyme genes. The TP53 tumour suppressor gene is an essential regulator of the cell-cycle arrest, DNA repair, and apoptosis (4). An important single nucleotide polymorphism detected in TP53 is Arg72Pro. This allele has been shown to decrease the activity of the corresponding protein, which is crucial for the apoptotic function of TP53 (5, 6). Recent studies have reported the association between this polymorphism and lung cancer (7-11).CYP2E1 is an important phase I biotransformation enzyme that transforms N-nitrosamines, vinyl chloride, and benzene in tobacco smoke into mutagenic and carcinogenic metabolites (12). In NSCLC patients it has been fou...

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“…One recent meta-analysis32 investigating the association between positive MDM2 expression and clinicopathological characteristics in patients with esophageal squamous cell carcinoma found that high MDM2 expression was associated with early primary tumor stage and increased risk of regional, but not distant, lymph node metastasis, whereas another study33 showed that loss of MTBP (MDM2 binding protein) expression may be linked to worse survival in some patients with SCCHN3233. In addition, the interaction between MDM2 and p53 , as well as several environmental factors, such as smoking, alcohol use, and HPV infection, may increase the risk of some squamous cell carcinomas423343536. For example, Chen et al .…”

Section: Discussionmentioning

confidence: 99%

Modifying effect of mouse double minute-2 promoter variants on risk of recurrence for patients with squamous cell carcinoma of oropharynx

Zhang

Wei

et al. 2017

Sci Rep

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Functional mouse double minute-2 (MDM2) promoter variants may alter MDM2 expression and thus affect radiotherapy response and prognosis of squamous cell carcinoma of oropharynx (SCCOP). Thus we assessed association of 2 functional MDM2 promoter variants with recurrence risk of SCCOP. The disease-free survival (DFS) of patients with MDM2rs2279744 TT or MDM2rs937283 AA genotypes was significantly reduced compared with that of patients with corresponding GT/GG or AG/GG genotypes. Multivariable analysis showed patients with TT or AA genotypes had a significantly higher risk of SCCOP recurrence than those with corresponding GT/GG or AG/GG genotypes did. Furthermore, patients with combined risk genotypes of the 2 polymorphisms had significantly worse DFS and a higher recurrence risk than patients with fewer combined risk genotypes did (Ptrend < 0.001). Compared with patients with 0 risk genotypes, patients with 1 or 2 risk genotypes had an approximately 3- or 11-fold increased risk of SCCOP recurrence, respectively. Notably, for both individual and combined polymorphisms, the above similar recurrence risks were particularly higher among patients with human papilloma virus (HPV)-positive tumors. Taken together, our findings suggest that MDM2 promoter variants individually, or more likely jointly, play a role in determining the risk of recurrence of SCCOP, particularly HPV-positive SCCOP.

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Association of Arg72Pro of TP53 and T309G of MDM2 genes polymorphisms with non-small-cell lung cancer in Russians of the Moscow region

Cited by 5 publications

References 15 publications

Influence of <em>MDM2</em> polymorphisms on squamous cell carcinoma susceptibility: a meta-analysis

Influence of <em>MDM2</em> polymorphisms on squamous cell carcinoma susceptibility: a meta-analysis

Association between the TP53 and CYP2E1*5B gene polymorphisms and non-small cell lung cancer

Modifying effect of mouse double minute-2 promoter variants on risk of recurrence for patients with squamous cell carcinoma of oropharynx

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