title: Modifying effect of mouse double minute-2 promoter variants on risk of recurrence for patients with squamous cell carcinoma of oropharynx.
abstract: 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.
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.|Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Beijing Institute of Otolaryngology, Beijing, 100730, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.|Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.|Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
authors.forename: Yuncheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.|Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Beijing Institute of Otolaryngology, Beijing, 100730, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.|Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D015987:Effect Modifier, Epidemiologic; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012306:Risk; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis
chemical_list: C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2