title: Significance of MDM2 and P14 ARF polymorphisms in susceptibility to differentiated thyroid carcinoma.
abstract: BACKGROUND
  Murine double minute 2 (MDM2) oncoprotein and p14(ARF) tumor suppressor play pivotal roles in regulating p53 and function in the MAPK pathway, which is mutated frequently in differentiated thyroid carcinoma (DTC). We hypothesized that functional polymorphisms in the promoters of MDM2 and p14(ARF) contribute to the interindividual difference in predisposition to DTC.
  
  
  METHODS
  MDM2-rs2279744, MDM2-rs937283, p14(ARF)-rs3731217, and p14(ARF)-rs3088440 were genotyped in 303 patients with DTC and 511 cancer-free healthy controls. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
  
  
  RESULTS
  MDM2-rs2279744 and p14(ARF)-rs3731217 were associated with a significantly increased risk of DTC (MDM2-rs2279744: TT versus TG/GG; OR, 1.5; 95% CI, 1.1-2.0; p14(ARF)-rs3731217: TG/GG versus TT; OR, 1.7; 95% CI, 1.2-2.3). No association was found for MDM2-rs937283 or p14(ARF)-rs3088440. Individuals carrying 3-4 risk genotypes of MDM2 and p14(ARF) had 2.2 times (95% CI, 1.4-3.5) the risk for DTC of individuals carrying 0-1 risk genotypes (P trend = .021). The combined effect of MDM2 and p14(ARF) on risk of DTC was confined to young subjects (≤ 45 years), nonsmokers, nondrinkers, and subjects with a first-degree family history of cancer. These associations were quite similar in strength when cases were restricted to those with papillary thyroid cancer.
  
  
  CONCLUSIONS
  Our results suggest that polymorphisms of MDM2 and p14(ARF) contribute to the interindividual difference in susceptibility to DTC, either alone or more likely jointly. The observed associations warrant further confirmation in independent studies.
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Xicheng
authors.initials: X
authors.lastname: Song
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics*; D018249:Adenoma, Oxyphilic; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics*; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D025803:Tumor Suppressor Protein p14ARF; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2