Yang Zhang1, Erich M Sturgis2, Yan Sun3, Chuanzheng Sun4, Qingyi Wei5, Zhigang Huang6, Guojun Li7. 1. 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; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 2. 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. 3. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Otorhinolaryngology and Head and Neck Surgery, Yuhuangding Hospital of Qingdao University, Yantai, China. 4. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Head and Neck Surgery, The Tumor Hospital of Yunnan Province, Kunming 650118, China. 5. Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA. 6. 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; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: enthzg@trhos.com. 7. 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. Electronic address: gli@mdanderson.org.
Abstract
BACKGROUND: Genetic polymorphisms in the 3' untranslated regions (3' UTRs) targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behaviour of individual miRNAs. An insertion (Ins)/deletion (Del) polymorphism (rs3783553) in the 3' UTR of IL-1α may disrupt a binding site for miRNA-122. IL-1α plays an important role in inflammation, immunity and defense against infection. Thus, we hypothesised that the rs3783553 polymorphism affects individual susceptibility to human papillomavirus (HPV)-associated oral squamous cell carcinoma (OSCC). METHODS: We genotyped the rs3783553 polymorphism; and determined HPV16 L1 serology, tumour HPV16 DNA and serum IL-1α expression. Univariate/multivariable logistic regression models were used to calculate associations. RESULTS: We found that HPV16 L1 seropositivity alone was associated with an increased risk of OSCC (Odds ratio (OR), 3.1; 95% confidence interval (CI), 2.1-4.6), and the risk of HPV16-associated OSCC was modified by the rs3783553 polymorphism. Patients with both HPV16 L1 seropositivity and Del/Del genotype for the rs3783553 had the highest risk of OSCC when using patients with HPV16 L1 seronegativity and Ins/Del+Ins/Ins genotypes as a comparison group. Notably, that effect modification was particularly pronounced in several subgroups (e.g. SCCOP, never-smokers and never-drinkers). The patients with Del/Del genotype were approximately 3.0 times more likely to have HPV16-positive squamous cell carcinoma of the oropharynx (SCCOP) tumours compared to those patients with Ins/Del+Ins/Ins genotypes. Additionally, functional relevance of this variant was characterised to explore the genotype-phenotype correlation. CONCLUSION: These results suggest that IL-1α 3' UTR rs3783553 polymorphism may be functional and influence susceptibility to HPV16-associated OSCC, particularly for SCCOP. Validation of our findings is warranted.
BACKGROUND: Genetic polymorphisms in the 3' untranslated regions (3' UTRs) targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behaviour of individual miRNAs. An insertion (Ins)/deletion (Del) polymorphism (rs3783553) in the 3' UTR of IL-1α may disrupt a binding site for miRNA-122. IL-1α plays an important role in inflammation, immunity and defense against infection. Thus, we hypothesised that the rs3783553 polymorphism affects individual susceptibility to human papillomavirus (HPV)-associated oral squamous cell carcinoma (OSCC). METHODS: We genotyped the rs3783553 polymorphism; and determined HPV16 L1 serology, tumourHPV16 DNA and serum IL-1α expression. Univariate/multivariable logistic regression models were used to calculate associations. RESULTS: We found that HPV16 L1 seropositivity alone was associated with an increased risk of OSCC (Odds ratio (OR), 3.1; 95% confidence interval (CI), 2.1-4.6), and the risk of HPV16-associated OSCC was modified by the rs3783553 polymorphism. Patients with both HPV16 L1 seropositivity and Del/Del genotype for the rs3783553 had the highest risk of OSCC when using patients with HPV16 L1 seronegativity and Ins/Del+Ins/Ins genotypes as a comparison group. Notably, that effect modification was particularly pronounced in several subgroups (e.g. SCCOP, never-smokers and never-drinkers). The patients with Del/Del genotype were approximately 3.0 times more likely to have HPV16-positive squamous cell carcinoma of the oropharynx (SCCOP) tumours compared to those patients with Ins/Del+Ins/Ins genotypes. Additionally, functional relevance of this variant was characterised to explore the genotype-phenotype correlation. CONCLUSION: These results suggest that IL-1α 3' UTR rs3783553 polymorphism may be functional and influence susceptibility to HPV16-associated OSCC, particularly for SCCOP. Validation of our findings is warranted.
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