The Journal of Experimental Medicine
Cytokines Montreal 2008
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Published online May 29, 2007
doi:10.1084/jem.20062476
The Journal of Experimental Medicine, Vol. 204, No. 6, 1295-1301
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Ørsted et al.
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BRIEF DEFINITIVE REPORT

 Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population

David Dynnes Ørsted1, Stig Egil Bojesen1,2, Anne Tybjærg-Hansen3,4, and Børge Grønne Nordestgaard1,3

1 Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
2 Department of Clinical Biochemistry and 3 The Copenhagen City Heart Study, Bispebjerg University Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark
4 Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark

CORRESPONDENCE Børge Grønne Nordestgaard: brno{at}heh.regionh.dk

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.

D. Dynnes Ørsted and S.E. Bojesen contributed equally to this paper.


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