title: Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal cancer patients after definitive radiotherapy.
abstract: Common single nucleotide polymorphisms (SNPs) in miRNAs may affect miRNA functions and their target expression and thus may affect biological activities and cancer etiology as well as prognosis. Thus, we determined whether the 9 SNPs in microRNAs modify the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP) in a cohort of 1008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. We found that the SNPs in the miRNA146, miRNA196, and Gemin3 were associated with a significantly reduced and increased risk of SCCOP recurrence after multivariate adjustment (aHR, 0.6, 95%CI, 0.4-0.9, aHR, 2.1, 95%CI, 1.6-2.8, and aHR, 0.6, 95%CI, 0.5-0.9, respectively). Furthermore, the similar effect of these 3 SNPs on SCCOP recurrence risk was found in HPV-positive SCCOP patients only. However, no significant associations were found for other SNPs. To evaluate the aggregate effects of these SNPs, we performed a combined risk genotype analysis. We found that, compared with the low-risk reference group with less than 4 risk genotypes, the medium-risk group with 4 or 5 risk genotypes exhibited a 1.7-fold (1.2-2.4) increased risk whereas the high-risk group with more than 5 risk genotypes exhibited a 3.0-fold (1.7-4.2) increased risk (Ptrend < 0.001). Such combined effects were particularly pronounced in HPV-positive SCCOP patients. Taken together, this is the first study with a large cohort of SCCOP patients showing that miRNA-related genetic variants may modify risk of SCCOP recurrence individually and jointly. Larger studies are needed to validate these results.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.|Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xingming
authors.initials: X
authors.lastname: Chen
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 Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.|Department of Otolaryngology-Head and Neck Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.|Department of Ultrasound, Yantai Yuhuangding Hospital, Yantai, 264000, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.|Department of Otolaryngology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 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 Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D055541:DEAD Box Protein 20 / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C542542:MIRN146 microRNA, human; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D055541:DEAD Box Protein 20
keywords: HPV; miRNA; oropharyngeal cancer; recurrence; variants