Association of combined p73 and p53 genetic variants with tumor HPV16-positive oropharyngeal cancer.
Abstract
p53 and p73 interact with human papillomavirus (HPV) E6 and E7 oncoproteins. The interplay
between p53 and p73 and HPV16 may lead to deregulation of cell cycle and apoptosis,
through which inflammation/immune responses control the HPV clearance and escape of
immune surveillance, and subsequently contribute to tumor HPV16 status. In this case-case
comparison study, HPV16 status in tumor specimens was analyzed and p53 codon 72 and
p73 G4C14-to-A4T14 polymorphisms were genotyped using genomic DNA from blood of 309
oropharyngeal cancer patients. Odds ratios (ORs) and 95% confidence intervals (95%
CIs) were calculated in univariate and multivariable logistic regression models to
examine the association. The results from this study showed both p53 variant genotypes
(Arg/Pro+Pro/Pro) and p73 variant genotypes (GC/AT+AT/AT) were significantly associated
with HPV16-positive tumor in oropharyngeal cancer patients (OR, 1.9, 95% CI, 1.1-3.3
and OR, 2.1, 95% CI, 1.2-3.8, respectively), while the combined variant genotypes
(p53 Pro carriers and p73 AT carriers) exhibited a significantly greater association
with HPV16-positive tumor (OR, 3.2, 95% CI, 1.4-7.4), compared with combined wild-type
genotypes (p53 Arg/Arg and p73 GC/GC), and the association was in a statistically
significant dose-effect relationship (p = 0.001). Moreover, such association was more
pronounced among several subgroups. These findings suggest that variant genotypes
of p53 and p73 genes may be individually, or more likely jointly, associated with
tumor HPV16-positive oropharyngeal cancer patients, particularly in never smokers.
Identification of such susceptible biomarkers would greatly influence on individualized
treatment for an improved prognosis.
Type
Journal articleSubject
HumansOropharyngeal Neoplasms
DNA-Binding Proteins
Tumor Suppressor Proteins
Nuclear Proteins
Logistic Models
Polymorphism, Genetic
Genes, p53
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Tumor Suppressor Protein p53
Human papillomavirus 16
Biomarkers, Tumor
Tumor Protein p73
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https://hdl.handle.net/10161/17980Published Version (Please cite this version)
10.1371/journal.pone.0035522Publication Info
Wang, Zhongqiu; Sturgis, Erich M; Guo, Wei; Song, Xicheng; Zhang, Fenghua; Xu, Li;
... Li, Guojun (2012). Association of combined p73 and p53 genetic variants with tumor HPV16-positive oropharyngeal
cancer. PloS one, 7(4). pp. e35522. 10.1371/journal.pone.0035522. Retrieved from https://hdl.handle.net/10161/17980.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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