Notes

The mechanisms that underlie the development of
CRC are complex, and both environmental and genetic
factors play important roles in the occurrence and
progression of this disease [50]. TP53 is crucial for proper
control of gene transcription, DNA synthesis and repair,
cell cycle arrest, senescence and apoptosis. Mutations
in TP53 can disrupt these functions, leading to genetic
instability and the progression to cancer.
In this meta-analysis, we found that the TP53
Arg72Pro polymorphism was not associated with CRC
in patients stratified based on type of CRC, genotype
method or source of controls. When stratified based on
ethnicity, there was a positive association between the
TP53 Arg72Pro polymorphism and CRC risk in Asian
populations, but not Caucasian or mixed populations.
These differences may reflect differences in genetic
background and/or environmental factors. The Arg72
variant of the TP53 Arg72Pro polymorphism is more
efficient with respect to mitochondrial localization than
the Pro72 variant and has a stronger capacity to induce
apoptosis [51]. Researchers observed that the Arg72 form
induced apoptosis with faster kinetics than did the Pro72
variant [52]. The greater apoptotic potential of the Arg72
protein stems from the greater interaction of this protein
with MDM2, which facilitates nuclear export [53]. The
two polymorphic variants of TP53 are functionally
distinct, and these differences may influence cancer risk
or treatment.

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Murphy M. The codon 72 polymorphic variants of p53
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52. Thomas M, Kalita A, Labrecque S, Pim D, Banks L,
Matlashewski G. Two polymorphic variants of wild-type
p53 differ biochemically and biologically. Mol Cell Biol.
1999;19:1092–100.
53. Boyd SD, Tsai KY, Jacks T. An intact HDM2 RING-finger
domain is required for nuclear exclusion of p53. Nat Cell
Biol. 2000;2:563–8.