%0 Journal Article
%T Effect of MDM2 SNP309 and p53 codon 72 polymorphisms on lung cancer risk and survival among non-smoking Chinese women in Singapore
%A Hui Chua
%A Daniel Ng
%A Serena Choo
%A San Lum
%A Huihua Li
%A Li Soh
%A Kanaga Sabapathy
%A Adeline Seow
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-88
%X We therefore examined the role of the SNPs in the p53 pathway (p53 codon 72 and MDM2 SNP309) on lung cancer risk and prognosis of a life-time non-smoking female Chinese population, in a hospital-based case-control study of 123 cases and 159 age-matched controls, by PCR analysis.Our findings reveal that the risk of lung cancer among individuals with the MDM2 SNP309 TT genotype was 2.1 (95% CI 1.01-4.36) relative to the GG genotype, contrary to initial expectations that the GG genotype with elevated MDM2 levels will increase cancer risk. Those who had this genotype in combination with the p53 Pro allele had a risk of 2.5 (95% CI 1.2-5.0). There was however no effect of either polymorphism on age at diagnosis of lung cancer or on overall survival.The results thus demonstrate that the MDM2 SNP309 TT rather than the GG genotype is associated with increased risk of lung cancer in this population, suggesting that other mechanisms independent of increased MDM2 levels can influence cancer susceptibility.The TP53 tumour suppressor pathway plays a critical role in cell cycle regulation and apoptosis in many cancers, including lung carcinomas [1], and variation in the genes that regulate this pathway may exert an important influence on tumour development, and hence, cancer risk. Recent interest has focused on the murine double minute-2 protein (MDM2), a nuclear phospoprotein that inhibits p53 activity by promoting its degradation [2]. A single nucleotide polymorphism (SNP309) in the MDM2 promoter has been found to influence transcription of this gene via a greater affinity for the SP1 transcription factor, and hence, individuals with the GG genotype have higher MDM2 levels leading to attenuation of the p53 pathway [3,4]. This has been especially so in the case of females, due to the involvement of the MDM2 SNP in the estrogen receptor signaling pathway [3].Several epidemiologic studies have evaluated this association with varying results. No overall association between MDM2 SNP
%U http://www.biomedcentral.com/1471-2407/10/88