A functional variant at miRNA-122 binding site in IL-1α 3′ UTR predicts risk and HPV-positive tumours of oropharyngeal cancer. Issue 11 (July 2015)

• Record Type: Journal Article
• Authors: Zhang, Yang; Sturgis, Erich M.; Sun, Yan; Sun, Chuanzheng; Wei, Qingyi; Huang, Zhigang; Li, Guojun
• Is Part Of: European journal of cancer. Volume 51:Issue 11(2015:Jul.)
• Page Start: 1415
• Page End: 1423
• Publication Date: 2015-07
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2015.04.016
• Languages: English
• ISSNs: 0959-8049

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title id="st005">Abstract</title> <sec> <title id="st010">Background</title> <p id="sp0005">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 <italic>IL-1α</italic> may disrupt a binding site for miRNA-122. <italic>IL-1α</italic> 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).</p> </sec> <sec> <title id="st015">Methods</title> <p id="sp0010">We genotyped the rs3783553 polymorphism; and determined HPV16 L1 serology, tumour HPV16 DNA and serum <italic>IL-1α</italic> expression. Univariate/multivariable logistic regression models were used to calculate associations.</p> </sec> <sec> <title id="st020">Results</title> <p id="sp0015">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.</p> </sec> <sec> <title id="st025">Conclusion</title> <p id="sp0020">These results suggest that <italic>IL-1α</italic> 3′ UTR rs3783553 polymorphism may be functional and influence susceptibility to HPV16-associated OSCC, particularly for SCCOP. Validation of our findings is warranted.</p> </sec> </abstract>