Abstract:
: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.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Li G,Zhai X,Zhang Z,Chamberlain RM,Spitz MR,Wei Qdoi
10.1093/carcin/bgl047subject
Has Abstractpub_date
2006-10-01 00:00:00pages
2028-33issue
10eissn
0143-3334issn
1460-2180pii
bgl047journal_volume
27pub_type
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