Abstract
Our genome has evolved to perpetuate itself through the maintenance of the species via an uninterrupted chain of reproductive somas. Accordingly, evolution is not concerned with diseases occurring after the soma's reproductive stage. Following Richard Dawkins, we would like to reassert that we indeed live as disposable somas, slaves of our germline genome, but could soon start rebelling against such slavery. Cancer and its relation to the TP53 gene may offer a paradigmatic example. The observation that the latency period in cancer can be prolonged in mice by increasing the number of TP53 genes in their genome, suggests that sooner or later we will have to address the question of heritable disease avoidance via the manipulation of the human germline.
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Selected References
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- DePinho R. A. The age of cancer. Nature. 2000 Nov 9;408(6809):248–254. doi: 10.1038/35041694. [DOI] [PubMed] [Google Scholar]
- Donehower L. A., Harvey M., Slagle B. L., McArthur M. J., Montgomery C. A., Jr, Butel J. S., Bradley A. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 1992 Mar 19;356(6366):215–221. doi: 10.1038/356215a0. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P. Cancer epigenetics takes center stage. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):392–394. doi: 10.1073/pnas.98.2.392. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finkel T., Holbrook N. J. Oxidants, oxidative stress and the biology of ageing. Nature. 2000 Nov 9;408(6809):239–247. doi: 10.1038/35041687. [DOI] [PubMed] [Google Scholar]
- García-Cao Isabel, García-Cao Marta, Martín-Caballero Juan, Criado Luis M., Klatt Peter, Flores Juana M., Weill Jean-Claude, Blasco María A., Serrano Manuel. "Super p53" mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J. 2002 Nov 15;21(22):6225–6235. doi: 10.1093/emboj/cdf595. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guarente L., Kenyon C. Genetic pathways that regulate ageing in model organisms. Nature. 2000 Nov 9;408(6809):255–262. doi: 10.1038/35041700. [DOI] [PubMed] [Google Scholar]
- Hahn William C., Weinberg Robert A. Modelling the molecular circuitry of cancer. Nat Rev Cancer. 2002 May;2(5):331–341. doi: 10.1038/nrc795. [DOI] [PubMed] [Google Scholar]
- Itahana K., Dimri G., Campisi J. Regulation of cellular senescence by p53. Eur J Biochem. 2001 May;268(10):2784–2791. doi: 10.1046/j.1432-1327.2001.02228.x. [DOI] [PubMed] [Google Scholar]
- Kumar Sudhir, Subramanian Sankar. Mutation rates in mammalian genomes. Proc Natl Acad Sci U S A. 2002 Jan 15;99(2):803–808. doi: 10.1073/pnas.022629899. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lippman Scott M., Hong Waun Ki. Cancer prevention by delay. Commentary re: J. A. O'Shaughnessy et al., Treatment and Prevention of Intraepithelial Neoplasia: An Important Target for Accelerated New Agent Development. Clin. Cancer Res., 8: 314-346, 2002. Clin Cancer Res. 2002 Feb;8(2):305–313. [PubMed] [Google Scholar]
- Nichols K. E., Malkin D., Garber J. E., Fraumeni J. F., Jr, Li F. P. Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol Biomarkers Prev. 2001 Feb;10(2):83–87. [PubMed] [Google Scholar]
- Oeppen Jim, Vaupel James W. Demography. Broken limits to life expectancy. Science. 2002 May 10;296(5570):1029–1031. doi: 10.1126/science.1069675. [DOI] [PubMed] [Google Scholar]
- Tyner Stuart D., Venkatachalam Sundaresan, Choi Jene, Jones Stephen, Ghebranious Nader, Igelmann Herbert, Lu Xiongbin, Soron Gabrielle, Cooper Benjamin, Brayton Cory. p53 mutant mice that display early ageing-associated phenotypes. Nature. 2002 Jan 3;415(6867):45–53. doi: 10.1038/415045a. [DOI] [PubMed] [Google Scholar]
- Vogelstein B., Lane D., Levine A. J. Surfing the p53 network. Nature. 2000 Nov 16;408(6810):307–310. doi: 10.1038/35042675. [DOI] [PubMed] [Google Scholar]
- Wubah J. A., Ibrahim M. M., Gao X., Nguyen D., Pisano M. M., Knudsen T. B. Teratogen-induced eye defects mediated by p53-dependent apoptosis. Curr Biol. 1996 Jan 1;6(1):60–69. doi: 10.1016/s0960-9822(02)00422-0. [DOI] [PubMed] [Google Scholar]