title: Combined effects of p73 and MDM2 polymorphisms on the risk of lung cancer.
abstract: p73, a structural and functional homologue of p53, plays an important role in modulating cell-cycle control and apoptosis. MDM2 represses the transcriptional activity of p73 and thus attenuates its activity. Based on the interaction between p73 and MDM2 in cell-cycle control and apoptosis, we investigated the association between p73 G4C14-to-A4T14 and MDM2 309T > G polymorphisms, alone and in combination, on the risk of lung cancer in a Korean population. The p73 and MDM2 genotypes were determined in 582 lung cancer patients and in 582 healthy control subjects who were frequency-matched for age and gender. The p73 AT/AT and MDM2 309 GG genotypes were associated with a nonsignificant increased risk of lung cancer (adjusted odds ratio [OR] = 1.37, 95% confidence interval [CI] = 0.83-2.24; and adjusted OR = 1.29, 95% CI = 0.92-1.80, respectively), compared with their wild-type genotypes, respectively. When the p73 and MDM2 polymorphisms were combined, the risk of lung cancer increased in a dose-dependent manner as the number of variant alleles increased (Ptrend = 0.01). Subjects with three or four variant alleles were at a significantly increased risk of lung cancer (adjusted OR = 1.74, 95% CI = 1.11-2.74, P = 0.02) compared to subjects with zero variant allele. These results suggest an additive effect of the p73 and MDM2 variant alleles on an increased risk of lung cancer.
authors.affiliation: Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Jun
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Park
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Jin Sung
authors.initials: JS
authors.lastname: Jang
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Kim
authors.forename: Sung Ick
authors.initials: SI
authors.lastname: Cha
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Kim
authors.forename: Sin
authors.initials: S
authors.lastname: Kam
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Jung
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002453:Cell Cycle; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2