A functional variant at miRNA-122 binding site in IL-1α 3’ UTR predicts risk of recurrence in patients with oropharyngeal cancer
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Chengyuan Wang1,2,*, Erich M. Sturgis1,3, Xingming Chen1,4,*, Qingyi Wei5, Guojun Li1,3
1Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2Department of Otolaryngology-Head and Neck Surgery, China-Japan Friendship Hospital, Beijing 100029, China
3Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
4Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
5Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA
*These authors contributed equally to this work and served as co-first authors
Guojun Li, e-mail: email@example.com
Keywords: IL1α, recurrence, oropharyngeal cancer, HPV, biomarker
Received: March 14, 2016 Accepted: April 07, 2016 Published: April 21, 2016
IL-1α, an important regulator of immune and inflammation responses, has been implicated in cancer development and prognosis. An insertion (Ins)/deletion (Del) polymorphism (IL-1α rs3783553) in the 3’ UTR of IL-1α may disrupt a binding site for miRNA-122 and may affect its transcription level. Thus, this polymorphism may cause interindividual variation in immune and inflammation responses and thus may lead to different susceptibility to treatment response and prognosis of such patients. We evaluated the association of IL-1α rs3783553 polymorphism with risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP) in a cohort of 1008 patients. Log-rank test and univariate and multivariable Cox models were used to evaluate associations. Compared with patients with Del/Del homozygous genotype, the patients with Ins/Del+Ins/Ins variant genotypes had worse disease-free survival (log-rank P < 0.0001) and increased risk of SCCOP recurrence (HR, 2.4, 95% CI, 1.7-3.3) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, the patients with Ins/Del+Ins/Ins variant genotypes of the IL-1α polymorphism had worse disease-free survival (log-rank P < 0.0001) and much higher recurrence risk than those with Del/Del homozygous genotype of this polymorphism (HR, 16.3, 95% CI, 5.0-52.7). Our findings suggest that IL-1α rs3783553 polymorphism may modulate the risk of SCCOP recurrence in patients, particularly for patients with HPV16-positive tumors. However, larger studies are needed to validate these results.
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