Combined effects of p73 and MDM2 polymorphisms on the risk of lung cancer.
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.
Jun
Hee Jung
HJ
Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.
Park
Sun Ha
SH
Lee
Won Kee
WK
Choi
Jin Eun
JE
Jang
Jin Sung
JS
Kim
Eun Jin
EJ
Cha
Sung Ick
SI
Kim
Dong Sun
DS
Kam
Sin
S
Kim
Chang Ho
CH
Kang
Young Mo
YM
Jung
Tae Hoon
TH
Park
Jae Yong
JY
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*
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