کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9879991 | 1534900 | 2005 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Variation in the human TP53 gene affects old age survival and cancer mortality1
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Gerontology - Volume 40, Issues 1â2, JanuaryâFebruary 2005, Pages 11-15
Journal: Experimental Gerontology - Volume 40, Issues 1â2, JanuaryâFebruary 2005, Pages 11-15
نویسندگان
Diana van Heemst, Simon P. Mooijaart, Marian Beekman, Jeroen Schreuder, Anton J.M. de Craen, Bernd W. Brandt, P. Eline Slagboom, Rudi G.J. Westendorp,