Risk of MDM2 SNP309 alone or in combination with the p53 codon 72 polymorphism in acute myeloid leukemia.
A single nucleotide polymorphism (SNP) in the promoter of MDM2 gene, SNP309 T>G (a T-G exchange at nucleotide 309 in the first intron), can increase the expression level of MDM2, thereby causing an impairment of p53 tumor suppressor activity. A G-C exchange at p53 codon 72 polymorphism results in a substitution of proline (Pro) for arginine (Arg) in the transactivation domain, which was shown to alter the primary structure of the p53 protein. Both polymorphisms have been implicated in cancer. To investigate whether that MDM2 SNP309 and p53 codon 72 polymorphism should be at least partially responsible for genetic susceptibility to acute myeloid leukemia (AML), both polymorphisms were determined in a case-control study consisting of 231 AML patients and 128 normal individuals. The MDM2 SNP309G allele was associated with increased risk of AML. Furthermore, the p53 codon 72 and MDM2 SNP309 polymorphisms did not associate with age of onset and any other clinical parameters studied. When the p53 and MDM2 polymorphisms were combined, no multiplicative joint effect between the MDM2 GG and p53 Pro/Pro genotypes exists in the risk of developing AML. These results suggest that the MDM2 SNP309 homozygous GG genotype may be a genetic susceptibility factor in the pathogenesis of AML.
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, People's Republic of China.
Xiujuan
X
Xiong
Min
M
Wang
Lin
L
Wang
Jiazhuo
J
Liu
Xin
X
Zhao
Zheng
Z
Tian
Jianxiang
J
Wang
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003062:Codon; D017931:DNA Primers; D005260:Female; D016158:Genes, p53; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D055815:Young Adult
D003062:Codon; D017931:DNA Primers; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2