title: Genetic variation in MDM2 and p14ARF and susceptibility to salivary gland carcinoma.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Xicheng
authors.initials: X
authors.lastname: Song
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012468:Salivary Gland Neoplasms / Q000235:genetics*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
chemical_list: D025803:Tumor Suppressor Protein p14ARF; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2