Genetic variants in the MDM2 promoter and p53 codon72 and lung cancer risk in non-smokers

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MDM2 is an important negative regulator of the p53 pathway, and high levels of this protein have been reported in preneoplastic and malignant lung lesions. A single nucleotide polymorphism (G2580T, or SNP309) in the promoter region of MDM2 has been identified, which is associated with enhanced expression in functional studies. We evaluated the influence of this polymorphism on lung cancer risk among Chinese women who are lifetime nonsmokers. A total of 162 primary lung cancer cases and 126 controls in a hospital-based case control study contributed genetic material for this analysis. The genotype frequency among controls in this population (TT, GT, GG) was 15.7%, 52.2% and 32.1%, respectively. The TT genotype conferred a 2-fold increase in risk relative to the GG genotype (adjusted odds ratio 2.1, 95% confidence interval 1.0-4.4), a finding at variance with studies in Western populations. TT individuals who also had the Arg/Pro or Pro/Pro genotype at the p53 codon 72 locus had an elevated risk (AOR 2.5, 1.2-5.0, p for interaction 0.06). Interestingly, the protective effect of high fruit and soy food intake on lung cancer was stronger in individuals with the MDM2 GG/GT genotype, but was abrogated by the TT genotype. Our results suggest that MDM2 and the p53 pathway may play a role in lung cancer among Asian female lifetime non-smokers, but the exact mechanisms are likely to differ from other populations and remain to be elucidated.