Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal cancer patients after definitive radiotherapy
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Xingming Chen1,2,*, Erich M. Sturgis2,3, Chengyuan Wang1,4,*, Xiaoli Cao1,5, Yuncheng Li1,6, Qingyi Wei7, Guojun Li2,3
1Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
2Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
3Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
4Department of Otolaryngology-Head and Neck Surgery, China-Japan Friendship Hospital, Beijing 100029, China
5Department of Ultrasound, Yantai Yuhuangding Hospital, Yantai, 264000, China
6Department of Otolaryngology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
7Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA
*These authors have contributed equally to this work
Guojun Li, e-mail: [email protected]
Keywords: miRNA, recurrence, oropharyngeal cancer, HPV, variants
Received: March 05, 2016 Accepted: April 15, 2016 Published: April 26, 2016
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.
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