TY - JOUR
T1 - MDM2 gene promoter polymorphisms and risk of lung cancer
T2 - A case-control analysis
AU - Li, Guojun
AU - Zhai, Xiaodong
AU - Zhang, Zhengdong
AU - Chamberlain, Robert M.
AU - Spitz, Margaret R.
AU - Wei, Qingyi
N1 - Funding Information:
We thank Margaret Lung and Peggy Schuber for assistance in recruiting the subjects; Li-E Wang, Zhaozheng Guo, Yawei Qiao, Jianzhong He and Kejin Xu for laboratory assistance; and Betty J.Larson and Joanne M.Sider for manuscript preparation and Chris J.Yeager for scientific editing. This study was supported in part by National Institutes of Health grants ES 11740 (to Q.W.), CA 57730 (to R.M.C.), CA55769 (to M.R.S.), Cancer Center Support Grant CA 16672, ES 11074 (to M.D. Anderson) and a Flight Attendants Medical Research Institute Professorship (to M.R.S.).
PY - 2006/10
Y1 - 2006/10
N2 - The MDM2 protein negatively regulates p53 expression level in modulating DNA repair, cell-cycle control, cell growth and apoptosis. Polymorphisms in the promoter region of the MDM2 gene have been shown to alter protein expression and may, thus, play a role in carcinogenesis. To test our hypothesis that the MDM2 promoter polymorphisms are associated with risk of lung cancer, we conducted a hospital-based, case-control study of 1026 non-Hispanic white patients newly diagnosed with lung cancer and 1145 cancer-free controls who were frequency-matched by age (±5 years), sex, ethnicity and smoking status. We genotyped for the MDM2 promoter G2580T (also called SNP309) and G2164A polymorphisms that have a minor allele frequency >0.05. The distributions of the MDM2- 2580G variant allele and genotypes were significantly less common among the cases than among the controls (P = 0.038 and 0.045, respectively), but this was not evident for MDM2- 2164G (P = 0.865 and 0.614, respectively). Compared with the MDM2- 2580TT genotype, the MDM2- 2580G variant genotypes were associated with a decreased risk of lung cancer [odds ratio = 0.81 and 95% confidence interval = 0.67-0.98 for GT, 0.83 (0.63-1.08) for GG, and 0.81 (0.68-0.97) for the combined GT/GG genotype]. However, no significant association was observed between the MDM2-2164G variant genotypes and lung cancer risk. Our results suggest that the MDM2-2580G allele may be a marker of reduced genetic susceptibility to lung cancer in the non-Hispanic white population, a finding that seems to contradict previous reports.
AB - The MDM2 protein negatively regulates p53 expression level in modulating DNA repair, cell-cycle control, cell growth and apoptosis. Polymorphisms in the promoter region of the MDM2 gene have been shown to alter protein expression and may, thus, play a role in carcinogenesis. To test our hypothesis that the MDM2 promoter polymorphisms are associated with risk of lung cancer, we conducted a hospital-based, case-control study of 1026 non-Hispanic white patients newly diagnosed with lung cancer and 1145 cancer-free controls who were frequency-matched by age (±5 years), sex, ethnicity and smoking status. We genotyped for the MDM2 promoter G2580T (also called SNP309) and G2164A polymorphisms that have a minor allele frequency >0.05. The distributions of the MDM2- 2580G variant allele and genotypes were significantly less common among the cases than among the controls (P = 0.038 and 0.045, respectively), but this was not evident for MDM2- 2164G (P = 0.865 and 0.614, respectively). Compared with the MDM2- 2580TT genotype, the MDM2- 2580G variant genotypes were associated with a decreased risk of lung cancer [odds ratio = 0.81 and 95% confidence interval = 0.67-0.98 for GT, 0.83 (0.63-1.08) for GG, and 0.81 (0.68-0.97) for the combined GT/GG genotype]. However, no significant association was observed between the MDM2-2164G variant genotypes and lung cancer risk. Our results suggest that the MDM2-2580G allele may be a marker of reduced genetic susceptibility to lung cancer in the non-Hispanic white population, a finding that seems to contradict previous reports.
UR - http://www.scopus.com/inward/record.url?scp=33749546905&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749546905&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgl047
DO - 10.1093/carcin/bgl047
M3 - Article
C2 - 16675470
AN - SCOPUS:33749546905
SN - 0143-3334
VL - 27
SP - 2028
EP - 2033
JO - Carcinogenesis
JF - Carcinogenesis
IS - 10
ER -