MDM2 SNP285 does not antagonize the effect of SNP309 in lung cancer

Ryan, Bríd M.; Calhoun, Kara; Pine, Sharon R.; Bowman, Elise D.; Robles, Ana I.; Ambs, Stefan; Harris, Curtis C.

doi:10.1002/ijc.27573

Cited by 21 publications

(33 citation statements)

References 25 publications

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“…In the study, the frequency of the MDM2 309G alleles among the controls was 0.544, which is almost identical to the frequency observed in the Japanese (0.525) (20), Han Chinese of southeast China (0.499) (14) and Korean (0.534) (16) populations; but is significantly higher compared to the Han Chinese of northeast China (0.455) (15), Caucasian (0.346-0.393) (11)(12)(13)18,38) and African-American (0.109-0.112) (13,38) populations (Fig. 1).…”

Section: Discussionsupporting

confidence: 73%

“…As an example of population heterogeneity, an interaction of c.309T>G with c.285G>C in the MDM2 gene was questionable (43), as it has been previously reported to act as an antagonist by overriding the effect of c.309T>G on Sp1-mediated transcription. However, the study by Ryan et al (38) recently reported that c.285G>C did not antagonize the effect of c.309T>G in lung cancer. Furthermore, the differences in frequencies of driver mutations, such as EGFR mutations (44), may contribute to the different effects of c.309T>G in various ethnic groups.…”

Section: T/t (%) T/g (%) G/g (%) T/t Vs G/g T/t Vs T/g+g/g T/t+t/g mentioning

confidence: 93%

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Single-nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk

et al. 2014

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Abstract. Murine double minute 2 (MDM2) is a negative regulator of p53. A single-nucleotide polymorphism (SNP) (rs2279744: c.309T>G) in the promoter region of the MDM2 gene has been shown to result in higher levels of MDM2 RNA and protein. Regarding the contribution of c.309T>G in the MDM2 gene to the lung cancer risk, previous studies are conflicting. In order to evaluate the association between c.309T>G and the lung cancer risk, a case-control study was performed. The MDM2 genotypes were determined in 762 lung cancer patients and in 700 cancer-free control subjects using the Smart Amplification Process. Statistical adjustment was performed for gender, age and pack-years of smoking. The distributions of c.309T>G (T/T, T/G, G/G) were 20.1, 49.7, 30.2% in the case group and 21.7, 47.9, 30.4% in the healthy-control group. There were no overall associations between the MDM2 genotypes and the risk of lung cancer [T/G genotype: Adjusted odds ratio (AOR), 1.30; 95% confidence interval (CI), 0.88-1.93; and G/G genotype: AOR, 1.18; 95% CI, 0.78-1.80]. The subgroup analysis of gender, histology, smoking status and epidermal growth factor receptor mutation status also indicated that there was no association with lung cancer. Additionally, the genotypes did not have an effect on the age at the time of diagnosis of lung cancer (P=0.25). In conclusion, the G allele frequency in the lung cancer cases was 0.551, which was similar to other studies. The results of the present study suggest that the c.309T>G is not significantly associated with lung cancer.

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Section: Discussionsupporting

confidence: 73%

Section: T/t (%) T/g (%) G/g (%) T/t Vs G/g T/t Vs T/g+g/g T/t+t/g mentioning

confidence: 93%

Single-nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk

et al. 2014

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“…However, recently, some reports [17,20] concluded that the T allele was a poor prognosis factor in Asians. Furthermore, three reports found no association between SNP309 and lung cancer survival in Asian [18,19], Caucasian and African-American [12].…”

Section: Mdm2 Snp309 and Lung Cancer Prognosesmentioning

confidence: 98%

“…SNP285 has been reported to nullify the effect of SNP309 and to reduced risk of breast, endometrial, and ovarian cancer. Molecular epidemiological studies of the c.309T>G polymorphisms in terms of lung cancer susceptibility [11][12][13] have yielded contradictory findings. We recently reported that c.309T>G was not associated with lung cancer susceptibility in a Japanese population [14].…”

Section: Mdm2 Snp309 and Lung Cancer Prognosesmentioning

confidence: 99%

“…We recently reported that c.309T>G was not associated with lung cancer susceptibility in a Japanese population [14]. The effects of c.309T>G on lung cancer survival have reported first in 2007 [15] and remain controversial [12,[15][16][17][18][19][20]. So far, seven studies have analyzed the association between c.309T>G of the MDM2 gene and lung cancer prognosis.…”

Section: Mdm2 Snp309 and Lung Cancer Prognosesmentioning

confidence: 99%

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Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma

et al. 2016

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The MDM 2 protein plays an important role in the regulation of cell proliferation and apoptosis via ubiquitination and proteasome‐mediated degradation of p53. The genetic polymorphism rs2279744 (c.309T>G) of the MDM 2 gene is reportedly associated with susceptibility and/or prognosis in various cancers. In this study, we investigated the risk factors for worse survival in patients with lung adenocarcinoma ( AC ). We examined the association between c.309T>G and the prognosis of lung cancer by retrospectively reviewing 453 lung cancer patients. We studied both, clinicopathological and genetic characteristics, including the c.309T>G, p53 Arg72Pro, EGFR , KRAS , and p53 mutations. Associations between these factors and survival outcome were analyzed using Cox proportional hazards models. The frequencies of MDM 2 polymorphisms were T/T, 20.8%; T/G, 48.6%, and G/G, 30.7%. The overall survival ( OS ) of AC patients with pathological stage I disease and the MDM 2 T/T genotype was significantly shorter than that of those with the T/G or G/G genotypes ( P = 0.02). Multivariate analysis revealed that the MDM 2 T/T genotype was an independent, significant prognostic factor (hazard ratio [ HR ] = 2.23; 95% confidence interval [ CI ]: 1.07–4.65; P = 0.03). The MDM 2 T/T genotype was predictive of poorer survival in a Japanese population. Genotyping for this polymorphism might predict the clinical outcomes of stage I AC patients.

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Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon

Gansmo

Knappskog

Romundstad

et al. 2014

Intl Journal of Cancer

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MDM2 is a key regulator of the p53 tumor suppressor protein and is overexpressed in many human cancers. Two single nucleotide polymorphisms (SNPs) located in the MDM2 intronic promoter (P2) have been found to exert biological function. The Gallele of SNP309T>G; rs2279744 increases MDM2 transcription and has been linked to increased cancer risk. In contrast, the less frequent SNP285G>C; rs117039649, which is in complete linkage disequilibrium with SNP309 (generating a SNP285C/ 309G variant haplotype), has been related to reduced MDM2 transcription and to reduced risk of breast, endometrial and ovarian cancer. In this large population-based case-control study, we genotyped SNP309 and SNP285 in 10,830 individuals, including cases with cancer of the breast (n51,717), colon (n51,532), lung (n51,331) and prostate (n52,501), as well as 3,749 non-cancer controls. We found a slightly reduced risk for lung cancer among individuals harboring the SNP309TG/GG genotypes compared to the SNP309TT genotype (OR5 0.86; CI 5 0.67-0.98), but this association was restricted to women (OR 5 0.77; CI 5 0.63-0.95) and was not present among men (OR 5 0.91; CI 5 0.77-1.08). Consistent with previous findings, we found a reduced risk for breast cancer among individuals carrying the SNP285GC/309GG genotype versus the SNP285GG/ 309GG genotype (OR 5 0.55; CI 5 0.33-0.93). In conclusion, our data support the hypothesis that the effects of both SNP285 and SNP309 status are tissue dependent.

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MDM2 SNP285 does not antagonize the effect of SNP309 in lung cancer

Cited by 21 publications

References 25 publications

Single-nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk

Single-nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk

Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma

Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon

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