p53 codon 72 genotype affects apoptosis by cytosine arabinoside in blood leukocytes

Haplotype structure and selection of the MDM2 oncogene in humans

“…As mentioned earlier, the p53-Pro isoform is weaker than p53-Arg in its ability to both suppress cellular transformation and induce apoptosis in cell culture (5)(6)(7)(8), and can associate with an earlier onset of tumor formation and a poorer tumor response to chemotherapy in humans (7,9,10). The data presented in this and previous reports suggest that Africans will have a very low frequency, if not zero, of the G allele of SNP309, whereas Caucasians and Asians will a much higher G allele frequency (14,16,21,22,24,33).…”

“…In the p53 gene, a SNP (codon 72) results in the change of a proline residue to an arginine at codon 72 of the p53 protein (p53-Pro and p53-Arg, respectively). Multiple groups have shown that p53-Pro is weaker than p53-Arg in its ability to both suppress cellular transformation and induce apoptosis in cell culture (5)(6)(7)(8), and can associate with an earlier onset of tumor formation and a poorer tumor response to chemotherapy in humans (7,9,10). In the MDM2 gene, a SNP (SNP309) results in a nucleotide change from the wild-type thymine (T) to guanine (G) in the intronic promoter/enhancer region (11).…”

Polymorphisms in the p53 pathway

“…These data are consistent with the hypothesis that the R72 allele, which has greater apoptotic ability, consequently possesses enhanced tumor suppression function. Also consistent with this hypothesis are findings that individuals with the R72 genotype have higher response rates and better survival after receiving chemo-and radiation therapy for advanced head and neck cancer (Sullivan et al, 2004) and for cancers of the breast and lung (Biros et al, 2002;Bonafe et al, 2002;Nelson et al, 2005;Tommiska et al, 2005;Xu et al, 2005). Therefore, while correlations between cancer risk and p53 polymorphic variants have not been clear, more consistent correlations exist for cancer progression, survival, age of onset, and response to therapy.…”

“…Two groups found that, for non-mutated forms of p53, the R72 variant has a significantly increased ability to induce programmed cell death, in cells containing inducible versions of p53, as well as in cells homozygous for R72 and P72 (Bonafe et al, 2002;Dumont et al, 2003). The absence of differences in specific DNA binding or transcriptional ability of these two polymorphic variants led our group to discover that the enhanced apoptotic potential of the R72 variant was owing to increased trafficking to the mitochondria, resulting from enhanced interaction with, and ubiquitylation by, the MDM2 ubiquitin ligase (Dumont et al, 2003).…”

Association between the TP53 Arg72Pro polymorphism and clinical outcomes in acute myeloid leukemia

“…The TP53 Arg72Pro polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism. 9 Details of the statistical analysis and clinical end points have been described previously.…”