p53 is an important tumor suppressor, normally preventing cancer development via apoptosis. A genomic Arg72Pro substitution in the p53 protein has important influence on cell death via apoptosis, which could be beneficial. We therefore tested the hypotheses that this polymorphism influences longevity, survival after a cancer diagnosis, and risk of cancer in the general population. We examined a cohort of 9,219 participants ages 20–95 from the Danish general population with 100% follow-up. The overall 12-yr survival was increased in p53 Arg/Pro heterozygotes with 3% (P = 0.003) and in Pro/Pro homozygotes with 6% (P = 0.002) versus Arg/Arg homozygotes, corresponding to an increase in median survival of 3 yr for Pro/Pro versus Arg/Arg homozygotes. We also demonstrated an increased survival after the development of cancer, or even after the development of other life-threatening diseases, for Pro/Pro versus Arg/Arg homozygotes. The Arg72Pro substitution did not associate with decreased risk of cancer. In conclusion, in this large cohort from the general population, we show that a well-known functional single nucleotide polymorphism in the tumor suppressor p53 protein leads to increased longevity, but not to decreased risk of cancer. The increased longevity may be due to increased survival after a diagnosis of cancer or other life-threatening diseases.
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11 June 2007
Brief Definitive Report|
May 29 2007
Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population
David Dynnes Ørsted,
David Dynnes Ørsted
1Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
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Stig Egil Bojesen,
Stig Egil Bojesen
1Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
2Department of Clinical Biochemistry
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Anne Tybjærg-Hansen,
Anne Tybjærg-Hansen
3The Copenhagen City Heart Study, Bispebjerg University Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark
4Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark
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Børge Grønne Nordestgaard
Børge Grønne Nordestgaard
1Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
3The Copenhagen City Heart Study, Bispebjerg University Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark
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David Dynnes Ørsted
1Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
Stig Egil Bojesen
1Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
2Department of Clinical Biochemistry
Anne Tybjærg-Hansen
3The Copenhagen City Heart Study, Bispebjerg University Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark
4Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark
Børge Grønne Nordestgaard
1Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
3The Copenhagen City Heart Study, Bispebjerg University Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark
CORRESPONDENCE Børge Grønne Nordestgaard: [email protected]
D. Dynnes Ørsted and S.E. Bojesen contributed equally to this paper.
Received:
November 27 2006
Accepted:
April 24 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (6): 1295–1301.
Article history
Received:
November 27 2006
Accepted:
April 24 2007
Citation
David Dynnes Ørsted, Stig Egil Bojesen, Anne Tybjærg-Hansen, Børge Grønne Nordestgaard; Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population . J Exp Med 11 June 2007; 204 (6): 1295–1301. doi: https://doi.org/10.1084/jem.20062476
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