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

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 (P_trend < 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.