Abstract
BackgroundSingle nucleotide polymorphism (SNP) 309 resulting in a T or G allele in the promoter of MDM2, the negative regulator of p53, has been suggested to affect cancer predisposition and age of onset, primarily in females. However, findings have been inconsistent in various cancers, and ethnicity appears to be a critical factor influencing the effects of the SNP on cancer risk. An increasing trend has been observed in the prevalence of lung cancers in non-smokers, especially females, though the underlying genetic basis is unclear.MethodsWe 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.ResultsOur 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.ConclusionsThe 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.
Highlights
Single nucleotide polymorphism (SNP) 309 resulting in a T or G allele in the promoter of murine double minute-2 protein (MDM2), the negative regulator of p53, has been suggested to affect cancer predisposition and age of onset, primarily in females
Other studies pointed to an interaction with smoking status no association was found between all lung cancers and the MDM2 SNP309, there was an elevated risk of cancer susceptibility in smokers compared to nonsmokers in the same study [10]
Because of the capacity of the polymorphism to enhance the inhibitory action of MDM2 on the p53 pathway, investigators have hypothesized that the GG genotype would negatively influence prognosis in lung cancer
Summary
Single nucleotide polymorphism (SNP) 309 resulting in a T or G allele in the promoter of MDM2, the negative regulator of p53, has been suggested to affect cancer predisposition and age of onset, primarily in females. No overall association between MDM2 SNP309 and lung cancer risk was observed in recent studies in a European [5], North American [6,7] and two Asian [8,9] populations. Other studies pointed to an interaction with smoking status no association was found between all lung cancers and the MDM2 SNP309, there was an elevated risk of cancer susceptibility in smokers compared to nonsmokers in the same study [10]. One study found that the risk of lung cancer was higher among individuals with the TT genotype - on stratification, this association was restricted to males and to smokers [12]. Two studies have demonstrated that the GG genotype is associated with a lower level of p53 expression [14] and with poorer survival [14,15]
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