Abstract
Cancers are often thought to be selectively neutral. This is because most of the individuals that they kill are post-reproductive. Some cancers, however, kill the young and so select for anticancer adaptations that reduce the chance of death. These adaptations could reduce the somatic mutation rate or the selective value of a mutant clone of cells, or increase the number of stages required for neoplasia. New theory predicts that cancer selection — selection to prevent or postpone deaths due to cancer — should be especially important as animals evolve new morphologies or larger, longer-lived bodies, and might account for some of the differences in the causes of cancer between mice and men.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Peto, R., Roe, F. J., Lee, P. N., Levy, L. & Clack, J. Cancer and ageing in mice and men. Br. J. Cancer 32, 411–442 (1975).
Nowell, P. C. The clonal evolution of tumor cell populations. Science 194, 23–28 (1976).
Vogelstein, B. & Kinzler, K. W. The multistep nature of cancer. Trends Genet. 9, 138–141 (1993).
Schlumberger, H. G. & Lucké, B. Tumors of fishes, amphibians and reptiles. Cancer Res. 8, 657–754 (1948).
Scharrer, B. & Lochhead, M. S. Tumors in the invertebrates: a review. Cancer Res. 10, 403–419 (1950).
Dawe, C. J. & Harshbarger, J. C. (eds). Neoplasms and Related Disorders in Invertebrates and Lower Vertebrate Animals. National Cancer Institute Monograph 31 (National Institutes of Health, Bethesda, Maryland, USA, 1969).
Montali, R. J. & Migaki G. (eds). Pathology of Zoo Animals (Smithsonian Institution Press, Washington DC, 1980).
Dawe, C. J., Harshbarger, J. C., Kondo, S., Sugimura, T. & Takayama. S. (eds). Phyletic Approaches to Cancer (Japan Scientific Societies Press, Tokyo, 1981).
Squires, D. F. Neoplasia in a coral. Science 148, 503–505 (1965).
Soule, J. D. Abnormal corallites. Science 150, 77 (1965).
Squires, D. F. Abnormal corallites: reply. Science 150, 78 (1965).
Finch, C. E. Longevity, Senesence and the Genome (Univ. Chicago Press, Chicago, 1990).
Rose, M. R. Evolutionary Biology of Aging (Oxford Univ. Press, Oxford, 1991).
Greaves, M. Cancer, The Evolutionary Legacy (Oxford Univ. Press, Oxford, 2000).
Graham, J. Cancer Selection: The New Theory of Evolution (Aculeus, Lexington, USA, 1992).
Schartl, M. Platyfish and swordtails: a genetic system for the analysis of molecular mechanisms in tumor formation. Trends Genet. 11, 185–189 (1995).
Adam, D., Dimitrijevic, N. & Schartl, M. Tumor suppression in Xiphophorus by an accidentally acquired promoter. Science 259, 816–819 (1993).
Nairn, R. S. et al. A CDKN2-like polymorphism in Xiphophorus LGV is associated with UV-B induced melanoma formation in platyfish-swordtail hybrids. Proc. Natl Acad. Sci. USA 93, 13042–13047 (1996).
Weis, S. & Schartl, M. The macromelanophore locus and the melanoma oncogene Xmrk are separate genetic entities in the genome of Xiphophorus. Genetics 149, 1909–1920 (1998).
Tjalma, R. A. Canine bone sarcoma: estimation of relative risk as function of body size. J. Natl Cancer Instit. 36, 1137–1150 (1966).
Withrow, S. J., Powers, B. E., Straw, R. C. & Wilkins, R. M. Comparative aspects of osteosarcoma: dog versus man. Clin. Orthop. 270, 159–168 (1991).
Smith, M. A. & Gloeckler Ries, L. A. in Principles and Practice of Pediatric Oncology 4th edn (eds Pizzo, P. A. & Poplack, D. G.) 1–12 (Lippincott Williams & Wilkins, Philadelphia, 2002).
DePinho, R. A. The age of cancer. Nature 408, 248–254 (2000).
Link, M. P., Gebhardt, M. C. & Meyers, P. A. in Osteosarcoma 4th edn (eds Pizzo, P. A. & Poplack, D. G.) 1051–1089 (Lippincott Williams & Wilkins, Philadelphia, 2002).
Fraumeni, J. F. Stature and malignant tumours of bone in childhood and adolesence. Cancer 20, 967–973 (1967).
Price, C. Primary bone-forming tumours and their relationship to skeletal growth. Br. J. Bone Joint Surg. 40, 574–593 (1958).
Bogin, B. Patterns of Human Growth (Cambridge Univ. Press, 1999).
Vanasse, G. J., Concannon, P. & Willerford, D. M. Regulated genomic instability and neoplasia in the lymphoid lineage. Blood 94, 3997–4010 (1999).
Nieuwenhuys, R., Ten Donkelaar, H. J. & Nicholson, C. The Central Nervous System of Vertebrates Vol. 3 (Springer, Berlin, 1998).
Cairns, J. Mutation selection and the natural history of cancer. Nature 255, 197–200 (1975).
Jenkins, P. J. & Besser, M. Acromegaly and cancer: a problem. J. Clin. Endocrinol. Metab. 86, 2935–2941 (2001).
Holly, J. M. P., Gunnell, D. J. & Davey Smith, G. Growth hormone, IGF-1 and cancer. Less intervention to avoid cancer? More intervention to prevent cancer? J. Endocrinol. 162, 321–330 (1999).
Eigenmann, J. E. Insulin-like growth factor in the dog. Front. Horm. Res. 17, 161–172 (1987).
Di Cristofano, A. et al. Pten is essential for embryonic development and tumour suppression. Nature Genet. 19, 348–355 (1998).
Varley, J. M., Evans, D. G. R. & Birch, J. M. Li–Fraumeni syndrome: a molecular and clinical review. Br. J. Cancer 76, 1–14 (1997).
Donehower, L. A. et al. Mice deficient for p53 are developmentaly normal but susceptible to spontaneous tumours. Nature 356, 215–221 (1992).
Jacks, T. et al. Tumour spectrum analysis in p53-mutant mice. Curr. Biol. 4, 1–7 (1994).
Jacks, T. Tumour suppressor gene mutations in mice. Ann. Rev. Genet. 30, 603–636 (1996).
Jacks, T. et al. Tumor predisposition in mice heterozygous for a targeted mutation in NF1. Nature Genet. 7, 353–361 (1994).
Brannan, C. I. et al. Targeted disruption of the neurofibromatosis Type 1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. Genes Dev. 8, 1019–1029 (1994).
Easton, D. F., Ford, D. & Bishop, D. T. Breast and ovarian cancer incidence in BRCA1 mutation carriers. Am. J. Hum. Genet. 56, 265–271 (1995).
Hakem, R. et al. The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse. Cell 85, 1009–1023 (1996).
Zhu, Y., Ghosh, P., Charnay, P., Burns, D. K. & Parada, L. F. Neurofibromas in NF1: Schwann cell origin and role of tumor environment. Science 296, 920–922 (2002).
Weaver, Z. et al. Mammary tumors in mice conditionally mutant for Brca1 exhibit gross genomic instability and centrosome amplification yet display a recurring distribution of genomic imbalances that is similar to human breast cancer. Oncogene 21, 5097–5107 (2002).
Andervort, H. B. & Dunn, T. B. Occurrence of tumors in wild house mice. J. Natl Cancer Instit. 28, 1153–1163 (1962).
Morris, J. & Dobson, J. Small Animal Oncology (Blackwell Science, Oxford, 2001).
King, R. J. B. Cancer Biology 2nd edn (Pearson Education, Harlow, UK, 2000).
Landy, R. B. in Pathology of Zoo Animals (eds Montali, R. J. & Migaki, G.) (Smithsonian Institution Press, Washington DC, 1980).
Dawe, C. J. in Neoplasms and Related Disorders in Invertebrates and Lower Vertebrate Animals. National Cancer Institute Monograph 31 (eds Dawe, C. J. C. J. & Harshbarger, J. C.) (National Institutes of Health, Bethesda, Maryland, USA, 1969).
Potten, C. S., Owen, G. & Booth, D. Intestinal stem cells protect their genome by selective segregation of template DNA strands. J. Cell Sci. 115, 2381–2388 (2002).
Cairns, J. Somatic stem cells and the kinetics of mutagenesis and carcinogenesis. Proc. Natl Acad. Sci. USA 99, 10567–10570 (2002).
Martin, G. M. et al. Somatic mutations are frequent and increase with age in human kidney epithelial cells. Hum. Mol. Genet. 5, 215–221 (1996).
Turker, M. S. Estimation of mutation frequencies in normal mammalian cells and the development of cancer. Semin. Cancer Biol. 8, 407–419 (1998).
Wu, X. & Pandolfi, P. P. Mouse models for multistep tumorigenesis. Trends Cell Biol. 11, S2–S9 (2001).
Nunney, L. Lineage selection and the evolution of multistage carcinogenesis. Proc. R. Soc. Lond. B. 266, 493–498 (1999)
Garcia-Cao, I. et al. 'Super p53' mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J. 21, 6225–6235 (2002).
Derry, W. B., Putzke, A. P. & Rothman, J. H. Caenorhabditis elegans p53: role in apoptosis, meiosis and stress resistance. Science 294, 591–595 (2001).
Yang, A., Kaghad, M., Caput, D. & McKeon, F. On the shoulders of giants: p63, p73 and the rise of p53. Trends Genet. 18, 91–96 (2002).
Armitage, P. & Doll, R. The age distribution of cancer and a multi-stage theory of carcinogenesis. Br. J. Cancer 8, 1–12 (1954).
Renan, M. J. How many mutations are required for tumorigenesis? Implications from human cancer data. Mol. Carcinog. 7, 139–146 (1993).
Pompei, F., Polkanov, M. & Wilson, R. Age distribution of cancer in mice: the incidence turnover at old age. Toxicol. Indust. Health 17, 7–16 (2001).
Hahn, W. C. & Weinberg, R. A. Modelling the molecular circuitry of cancer. Nature Rev. Cancer 2, 331–341 (2002).
Hemann, M. T. & Greider, C. W. Wild-derived inbred mouse strains have short telomeres. Nucl. Acids Res. 28, 4474–4478 (2000).
Robanus Maandag, E. et al. p107 is a suppressor of retinoblastoma development in pRb-deficient mice. Genes Dev. 12, 1599–1609 (1998).
Classon, M. & Harlow, E. The retinoblastoma tumour suppressor in development and cancer. Nature Rev. Cancer 2, 910–917 (2002).
Lowe, C. & Goodman–Lowe, G. Suntanning in hammerhead sharks. Nature 383, 677 (1996).
Frame, S. et al. Epithelial carcinogenesis in the mouse: correlating the genetics and the biology. Phil. Trans. R. Soc. Lond. B 353, 839–845 (1998).
Heddle, J. A., Cosentino, L., Dawood, G., Swiger, R. R. & Paashuis-Lew, Y. Why do stem cells exist? Environ. Molec. Mut. 28, 334–341 (1996).
Bergers, G. et al. Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science 284, 808–812 (1999).
Das, U. & Das, A. K. Review of canine transmissible venereal sarcoma. Vet. Res. Commun. 24, 545–556 (2000).
Choi, Y. et al. Molecular structure of canine LINE-1 elements in canine transmissible venereal tumor. Anim. Genet. 30, 51–53 (1999).
Acknowledgements
We thank C. Isacke and M. Schartl for commenting on drafts of the manuscript. We also thank A. Ashworth, J. Barnes, F. Pompei, M. Schartl and W. Weber for answering queries and providing the figures. Our research was supported by the Biotechnology and Biological Sciences Research Council (UK), Natural Environmental Research Council (UK), the Wellcome Trust and the Daphne Jackson Trust (UK).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Leroi, A., Koufopanou, V. & Burt, A. Cancer selection. Nat Rev Cancer 3, 226–231 (2003). https://doi.org/10.1038/nrc1016
Issue Date:
DOI: https://doi.org/10.1038/nrc1016
This article is cited by
-
The Mystery of Cancer Resistance: A Revelation Within Nature
Journal of Molecular Evolution (2023)
-
Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum
Genome Biology (2022)
-
Cancer risk across mammals
Nature (2022)
-
TERT promoter alterations could provide a solution for Peto’s paradox in rodents
Scientific Reports (2020)
-
How is the evolution of tumour resistance at organ-scale impacted by the importance of the organ for fitness?
BMC Evolutionary Biology (2018)