Is MDM2 SNP309 Variation a Risk Factor for Head and Neck Carcinoma?

Abstract

Murine double minute-2 (MDM2) is a negative regulator of P53, and its T309G polymorphism has been suggested as a risk factor for a variety of cancers. Increasing evidence has shown the association of MDM2 T309G polymorphism with head and neck carcinoma (HNC) risk. However, the results are inconsistent. Thus, we performed a meta-analysis to elucidate the association.The meta-analysis retrieved studies published up to August 2015, and essential information was extracted for analysis. Separate analyses on ethnicity, source of controls, sample size, detection method, and cancer types were also conducted. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate the association.Pooled data from 16 case–control studies including 4625 cases and 6927 controls failed to indicate a significant association. However, in the subgroup analysis of sample sizes, an increased risk was observed in the largest sample size group (>1000) under a recessive model (OR = 1.52; 95% CI = 1.08–2.13). Increased risks were also found in the nasopharyngeal cancer in the subgroup analysis of cancer types (GG vs TT: OR = 2.07; 95% CI = 1.38–3.12; dominant model: OR = 1.48; 95% CI = 1.13–1.93; recessive model: OR = 1.76; 95% CI = 1.17–2.65).The results suggest that homozygote GG alleles of MDM2 SNP309 may be a low-penetrant risk factor for HNC, and G allele may confer nasopharyngeal cancer susceptibility.

Combined Effect of HPV and Several Gene SNPs in Laryngeal Cancer

“…Difference between survival groups was not significant, but MDM2 T/T survival was 65.6% and T/G survival was 46.0% at 1631 days' post-surgical operation (p = 0.13). Zhua X. et al results indicate that homozygous G/G alleles of MDM2 SNP309 may be a low-penetrant risk factor for HNSCC, and G allele may confer nasopharyngeal Canter susceptibility [26]. Data were confirmed in the Asian population: in a study of 103 patients, the G/G genotype of MDM2 SNP309 was associated (p = 0.032) with an earlier onset of HNSCC.…”

“…Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism [24]. The C677T SNP in MTHFR (rs1801133), which regulates the release of active folate in the body, may have reduced activity [25,26]. Epidemiological evidence suggests that the SNPs encoding the enzymes involved in folate metabolism may increase the risk of head and neck cell carcinoma (HNSCC) by altering DNA methylation synthesis and genomic stability [25].…”

“…Epidemiological evidence suggests that the SNPs encoding the enzymes involved in folate metabolism may increase the risk of head and neck cell carcinoma (HNSCC) by altering DNA methylation synthesis and genomic stability [25]. Given that folate participates in intracellular pathways, it seems plausible that patients with HNSCC may respond differently to treatments, based on genetic SNP [25,26].…”

CLINICAL IMPLICATIONS OF p53 ALTERATIONS IN ORAL CANCER PROGRESSION: A REVIEW FROM INDIA

“…However, authors suggested that this polymorphism may modulate cancer risk in combination with p53 and p73 polymorphisms. More interestingly, a recent meta-analysis by Zhuo et al [57] also suggested that homozygote GG alleles of MDM2 SNP309 may be a low-penetrant risk factor for HNC, and G allele may confer nasopharyngeal cancer susceptibility.…”

Major Molecular Signaling Pathways in Oral Cancer Associated With Therapeutic Resistance

“…Based on this tightly balanced negative feedback mechanism; it is understandable that any genetic polymorphism in MDM2 can also alter p53 functional levels. A number of reports have highlighted this fact in oral cancers especially via one intronic polymorphism (rs2279744) in MDM2 leading to its induced expression [ 26 ].…”