MDM2 SNP309 G allele decreases risk but does not affect onset age or survival of Chinese leukaemia patients.
Although mutations in p53 are rare in leukaemia, MDM2, the negative regulator of p53, is often overexpressed. Recently, a single nucleotide polymorphism (SNP) in the MDM2 promoter--within the oestrogen-receptor-binding region--resulting in either a G or T allele was shown to affect its transcription, with elevated MDM2 being produced when it is a G allele. Expectedly, SNP309G females were found to be at a higher risk of accelerated onset of cancers. We have therefore analysed, in a pilot study, whether the status of MDM2 SNP309 and p53 codon-72 polymorphism, which was also shown to affect cancer predisposition, would affect cancer risk, onset age, overall survival and response to therapy in Chinese leukaemia patients. p53 SNP was not associated with any of the parameters. However, in contrast to expectations, the MDM2 SNP309G allele was associated with reduced risk of leukaemia. No other association was found between SNP309 and other parameters in both males and females. Thus, the data highlights ethnic differences in the effects of this SNP on cancer risk.
Phang
Beng Hooi
BH
Division of Cellular & Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 11 Hospital Drive, Singapore, Singapore.
Linn
Yeh Ching
YC
Li
Huihua
H
Sabapathy
Kanaga
K
D000328:Adult; D017668:Age of Onset; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002681:China / Q000453:epidemiology; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D016019:Survival Analysis
D000970:Antineoplastic Agents; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2