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Combined effects of p73 and MDM2 polymorphisms on the risk of lung cancer
Author(s) -
Jun Hee Jung,
Park Sun Ha,
Lee Won Kee,
Choi Jin Eun,
Jang Jin Sung,
Kim Eun Jin,
Cha Sung Ick,
Kim Dong Sun,
Kam Sin,
Kim Chang Ho,
Kang Young Mo,
Jung Tae Hoon,
Park Jae Yong
Publication year - 2007
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20279
Subject(s) - lung cancer , biology , odds ratio , allele , genotype , mdm2 , confidence interval , medicine , case control study , cancer , oncology , lower risk , apoptosis , cancer research , genetics , gene
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 ( P trend = 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. © 2006 Wiley‐Liss, Inc.