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.
Type
Journal articleSubject
HumansCarcinoma, Squamous Cell
Head and Neck Neoplasms
Oropharyngeal Neoplasms
Neoplasm Recurrence, Local
Genetic Predisposition to Disease
MicroRNAs
Disease-Free Survival
Proportional Hazards Models
Genotype
Polymorphism, Single Nucleotide
Adult
Aged
Middle Aged
Female
Male
DEAD Box Protein 20
Kaplan-Meier Estimate
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https://hdl.handle.net/10161/18002Published Version (Please cite this version)
10.18632/oncotarget.9014Publication Info
Chen, Xingming; Sturgis, Erich M; Wang, Chengyuan; Cao, Xiaoli; Li, Yuncheng; Wei,
Qingyi; & Li, Guojun (2016). Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal
cancer patients after definitive radiotherapy. Oncotarget, 7(23). pp. 35015-35025. 10.18632/oncotarget.9014. Retrieved from https://hdl.handle.net/10161/18002.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Qingyi Wei
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director
for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology
and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally
recognized epidemiologist focused on the molecular and genetic epidemiology of head
and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and
genetic determinants for the DNA repair deficient phenotype and

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