Genetic variation in MDM2 and p14ARF and susceptibility to salivary gland carcinoma.
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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.
Salivary Gland Neoplasms
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Tumor Suppressor Protein p14ARF
Proto-Oncogene Proteins c-mdm2
Published Version (Please cite this version)10.1371/journal.pone.0049361
Publication InfoJin, 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.
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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