title: Role of the MDM2 SNP309 polymorphism in the initiation and early age of onset of nasopharyngeal carcinoma.
abstract: Recent studies refer that amplification/overexpression of the principal negative regulator of p53 (Mdm2) is frequently found in several malignancies. Several studies have associated a polymorphism (SNP309 T/G) in the promoter region of MDM2 with higher levels of this protein, which will favor p53-pathway abolishment, cell-cycle escape, and development of cancer. We aimed to study if MDM2 SNP309 T/G polymorphism contributes to the development of nasopharyngeal carcinoma (NPC). We have developed a case-control study with 124 patients with NPC and 509 healthy individuals from the north of Portugal to determine the genetic distribution of the MDM2 SNP309 polymorphism in DNA extracted from peripheral blood samples. Statistical analysis was performed to compare categorical variables adjusted for age and gender by multivariate logistic regression. Genotype-specific distributions according to age of onset were tested by Kaplan-Meier method and analyzed by Cox-regression proportional hazard model adjusted for gender. This study revealed that MDM2 SNP309 GG homozygous represent an increased risk adjusted for age and gender to develop NPC (OR = 2.15), with particular effect in undifferentiated types (OR = 2.46) and early clinical stages (OR = 3.32). We also found that median age of onset of NPC was significantly different (55.2 vs. 61.6) with increased effect in undifferentiated types (55.2 vs. 61.9) and early clinical stages (55.3 vs. 65.3). Our study suggests that MDM2 SNP309 can be considered a risk marker for the development of NPC mainly in early ages probably as an initiation marker for potential cancer development.
authors.affiliation: Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Porto, Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Sousa
authors.forename: Mafalda
authors.initials: M
authors.lastname: Pando
authors.forename: Eduardo
authors.initials: E
authors.lastname: Breda
authors.forename: Raquel
authors.initials: R
authors.lastname: Catarino
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
mesh_terms: D000328:Adult; D017668:Age of Onset; D002277:Carcinoma; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012306:Risk; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2