title: E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx.
abstract: Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been implicated in carcinogenesis and prognosis, we investigated associations between genetic variants in five E2F2 promoter polymorphisms and recurrence risk of squamous cell carcinoma of the oropharynx (SCCOP) in 1 008 patients. A log-rank test and multivariable Cox models were used to assess the associations. Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous genotypes had better disease-free survival (both log-rank, P < 0.001) and lower SCCOP recurrence risk (HR, 0.4, 95% CI, 0.3-0.6 and HR, 0.3, 95% CI, 0.2-0.5, respectively) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, those with common homozygous genotypes of E2F2-rs2742976 and E2F2-rs3218123 had better disease-free survival rates (both log-rank, P < 0.001) and lower recurrence risk (HR, 0.1, 95% CI, 0.1-0.4 and HR, 0.1, 95% CI, 0.0-0.2, respectively) than patients with variant genotypes. However, no significant differences were found for the other three polymorphisms. After combining the risk genotypes of the five polymorphisms and using the high-risk group (2-5 risk genotypes) as the reference group, we found that the low-risk groups (0 or 1 risk genotype) had significantly lower recurrence risk among all patients (HR, 0.4, 95% CI, 0.3-0.6) and among HPV16-positive patients (HR, 0.2, 95% CI, 0.1-0.5). Our findings suggest that E2F2 polymorphisms may individually or jointly modify SCCOP recurrence risk, particularly for SCCOP patients with HPV16-positive tumors. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science Technology, Wuhan, China.|Department of Head Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yuncheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Head Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.affiliation: Department of Head Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Oral Maxillofacial Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Head Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Ultrasound, Yantai Yuhuangding Hospital, Yantai, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Cao
authors.affiliation: Duke University Medical Center, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Head Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Otorhinolaryngology-Head and Neck Surgery, Yuhuangding Hospital of Qingdao University, Yantai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Head Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D018572:Disease-Free Survival; D050703:E2F2 Transcription Factor / Q000235:genetics*; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D009960:Oropharynx / Q000378:metabolism / Q000473:pathology*; D030361:Papillomavirus Infections / Q000150:complications; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor; D050703:E2F2 Transcription Factor
keywords: E2F2 variant genotypes; human papillomavirus; oropharyngeal cancer; predictive biomarkers; recurrence