Genetic variation in MDM2 and p14ARF and susceptibility to salivary gland carcinoma.
Abstract
The p14(ARF)/MDM2/p53 pathway plays an important role in modulation of DNA damage
and oxidative stress responses. The aim of this study was to determine whether genetic
variants in MDM2 and p14(ARF) are associated with risk of salivary gland carcinoma
(SGC).Four single nucleotide polymorphisms (SNPs) in MDM2 and p14(ARF) (MDM2-rs2279744,
MDM2-rs937283, p14(ARF)-rs3731217, and p14(ARF)-rs3088440) were genotyped in 156 patients
with SGC and 511 cancer-free controls. Multivariate logistic regression analysis was
performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs).MDM2-rs2279744
was significantly associated with a moderately increased risk of SGC (OR, 1.5, 95%
CI, 1.1-2.2). There was a trend toward significantly increased SGC risk with increasing
number of risk genotypes of the four polymorphisms (P(trend) = 0.004). Individuals
carrying 3-4 risk genotypes in MDM2 and p14(ARF) were at increased SGC risk (OR, 2.0,
95% CI, 1.1-2.7) compared with individuals carrying 0-2 risk genotypes. Moreover,
the combined effect of risk genotypes of MDM2 and p14(ARF) was more pronounced among
young subjects (≤ 45 years), female subjects, subjects with race/ethnicity other than
non-Hispanic white, ever-smokers, and ever-drinkers.Our results support the involvement
of SNPs of MDM2 and p14(ARF), either alone or more likely in combination, in susceptibility
to SGC. Larger studies are needed to validate our findings.
Type
Journal articleSubject
HumansCarcinoma
Salivary Gland Neoplasms
Genetic Predisposition to Disease
Multivariate Analysis
Confidence Intervals
Logistic Models
Odds Ratio
Case-Control Studies
Genotype
Polymorphism, Single Nucleotide
Adult
Middle Aged
Female
Male
Tumor Suppressor Protein p14ARF
Proto-Oncogene Proteins c-mdm2
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https://hdl.handle.net/10161/17985Published Version (Please cite this version)
10.1371/journal.pone.0049361Publication Info
Jin, Lei; Xu, Li; Song, Xicheng; Wei, Qingyi; Sturgis, Erich M; & Li, Guojun (2012). Genetic variation in MDM2 and p14ARF and susceptibility to salivary gland carcinoma.
PloS one, 7(11). pp. e49361. 10.1371/journal.pone.0049361. Retrieved from https://hdl.handle.net/10161/17985.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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