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• W2037024229 abstract "Longevity may depend on a balance between tumor suppression and tissue renewal mechanisms [Campisi, J., 2003. Cancer and ageing: rival demons? Nat. Rev. Cancer 3 (5), 339–349]. Mice with constitutively activated p53 are almost cancer free but their life span is reduced and accompanied by early tissue atrophy [Tyner et al., 2002. p53 mutant mice that display early ageing-associated phenotypes. Nature 415 (6867), 45–53]. Replacement of arginine (Arg) by proline (Pro) at position 72 of human p53 decreases its apoptotic potential [Dumont et al., 2003. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat. Genet. 33 (3), 357–365] providing a tool to test for a similar trade-off in humans. Using a formal meta-analysis of the published literature we show that carriers of the TP53 codon 72 Pro/Pro genotype have an increased cancer risk compared to Arg/Arg carriers (p<0.05). Next, in a prospective study of 1226 people aged 85 years and over we show that carriers of the Pro/Pro genotype have a 41% increased survival (p=0.032) despite a 2.54 fold increased (p=0.007) proportional mortality from cancer. It is suggested that human p53 protect against cancer but at a cost of longevity." @default.
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• W2037024229 date "2005-01-01" @default.
• W2037024229 modified "2023-10-12" @default.
• W2037024229 title "Variation in the human TP53 gene affects old age survival and cancer mortality" @default.
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• W2037024229 doi "https://doi.org/10.1016/j.exger.2004.10.001" @default.
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