A TGF-β1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16-associated oropharyngeal cancer.
Abstract
TGF-β1rs1982073 polymorphism at the miRNA-187 binding site may alter TGF-β1 expression
and function, and thereby this polymorphism (genotype CT/CC) increases cancer susceptibility.
HPV16 L1 seropositivity is associated with the risk of oral squamous cell carcinoma
(OSCC), including oropharyngeal squamous cell carcinoma (OPSCC) and oral cavity squamous
cell carcinoma (OCSCC). Thus, we hypothesized that TGF-β1rs1982073 polymorphism at
the miRNA-187 binding site combined with HPV16 L1 seropositivity may have a joint
effect on OSCC susceptibility. We determined the genotypes of TGF-β1rs1982073 and
HPV16 status in 325 OSCC subjects and 335 cancer-free controls in the non-Hispanic
white population, and used logistic regression models to evaluate the joint effects
on OSCC susceptibility. TGF-β1rs1982073 polymorphism (CT/CC genotype) combined with
HPV16 L1 seropositivity increased the risk of OSCC via joint effects, particularly
in OPSCC subjects who were never-smokers (OR, 165.9; 95% CI, 28.6-960.4) or never-drinkers
(OR, 196.0; 95% CI, 28.2-1,000.0), respectively. Younger subjects had a higher risk
of OPSCC than older subjects (OR, 23.5; 95% CI, 6.3-87.0 vs. OR, 6.0; 95% CI, 1.7-17.9,
respectively). The significant associations between this polymorphism and HPV16-associated
OSCC and OPSCC were also observed. However, OCSCC subjects did not have similar results.
Our findings suggest that the joint effects of TGF-β1rs1982073 and HPV16 L1 seropositivity
can increase risk of HPV16-associated oral cancer, particularly in OPSCC subjects
who are never-smokers, never-drinkers and young. This result may help us understand
the tumorigenesis process and improve early detection, which are critical for prevention
and intervention strategies. However, larger studies are needed to validate our findings.
Type
Journal articleSubject
HumansPapillomavirus Infections
Carcinoma, Squamous Cell
Oropharyngeal Neoplasms
Genetic Predisposition to Disease
Oncogene Proteins, Viral
Capsid Proteins
MicroRNAs
Prognosis
Case-Control Studies
Follow-Up Studies
Binding Sites
Genotype
Polymorphism, Single Nucleotide
Middle Aged
Female
Male
Human papillomavirus 16
Transforming Growth Factor beta1
Biomarkers, Tumor
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https://hdl.handle.net/10161/18504Published Version (Please cite this version)
10.1002/ijc.31530Publication Info
Tao, Ye; Sturgis, Erich M; Huang, Zhigang; Sun, Yan; Dahlstrom, Kristina R; Wei, Qingyi;
& Li, Guojun (2018). A TGF-β1 genetic variant at the miRNA187 binding site significantly modifies risk
of HPV16-associated oropharyngeal cancer. International journal of cancer, 143(6). pp. 1327-1334. 10.1002/ijc.31530. Retrieved from https://hdl.handle.net/10161/18504.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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