Petos Parodoxon

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The English term Peto's paradox - the German translation of Peto's paradox has not yet found widespread use in German-language specialist literature - is a contradiction in the field of oncology named after the British statistician and epidemiologist Richard Peto .

The paradox arises from the consideration that with the increase in the number of body cells, the probability of malignant degeneration increases proportionally and therefore large mammals would have to develop cancer much more frequently than small mammals. In fact, the incidence of cancer in mammals differs only slightly. Peto formulated these considerations in 1975.

The boundary conditions

A blue whale has about 100 million times the mass (200 tons) of a pig-nosed bat and is the largest mammal on earth.

All vertebrate species are believed to be affected by cancer . Apparently , these malignant tissue changes are most common in mammals. The basic mechanisms that can lead to cancer are very similar in all mammalian species. Many mechanisms for suppressing tumors, such as tumor suppressor genes , are also present in all mammals. Among other things, this enables mammals to be used as model organisms in cancer research in human cancer. In terms of cellular structure, metabolism and reproduction, the mammalian class - from the two-gram pig- nosed bat ( Craseonycteris thonglongyai ) to the 100 million times heavier blue whale (200 tons) - has a lot in common.

In mammals, the cancer rate varies by a factor of about 2. In all known mammals, cancers occur in significant numbers and in many cases also lead to the death of the affected individuals . Reliable figures on cancer rates are available for various model organisms. In contrast, there is relatively little data on mammals living in the wild . In house mice ( Mus musculus ) reared in the laboratory , around 46% developed tumors when they died. In dogs ( Canis lupus familiaris ) it is approximately 20% and in humans it is 22% (in the US , cancer-related deaths). Cases of cancer are also known in blue whales ( Balaenoptera musculus ). Statistical figures are not available, but it is assumed that most whales will not die of cancer. The investigation of 2000 hunted baleen whales ( Mysticeti ) in 1966 in Saldanha Bay found no evidence of cancer.

In the autopsy of 129 of the total of 263 dead beluga whales stranded on the banks of the Saint Lawrence River between 1983 and 1999, cancer was found in 27% of the cases and the primary cause of death in 18%. This rate is extremely high for whales and has not been found in any other whale population. The cause is suspected to be the pollution of the river estuary through industrial and agricultural production.

According to the theory of carcinogenesis ( carcinogenesis ) recognized by evidence-based medicine , the first disease event takes place at the cellular level. This transforms a normal body cell into a malignant tumor cell.

The paradox

Larger organisms have a higher number of body cells. As the number of cells increases, the likelihood that one of them will degenerate into a malignant tumor cell increases. Accordingly, such organisms should have a higher number of potential cancer cells and therefore develop cancer much more frequently and faster than small organisms. In addition, larger organisms live longer and require considerably more cell divisions for ontogenesis in order to develop from the fertilized egg cell to the adult animal. These are also factors that should significantly increase the likelihood of degenerate cells forming in larger organisms. Based on these considerations, there should be a correlation between cancer incidence and body mass in mammals. In fact, there is no evidence of such a correlation.

Hypotheses to explain the paradox

Several hypotheses to explain Peto's paradox have been put forward and are controversial: Some scientists assume that the mutation rate in mammals depends on their size. Large mammals have a lower mutation rate than small mammals. The different mutation rates would have evolutionary causes.

Other researchers assume that the repair mechanisms and the immune system of large mammals are better developed than in small mammals, which means that the larger mammals have a higher resistance.

Other working groups assume that, as the living being becomes larger, cancer tumors themselves can reach growth limits that are detrimental to them. The lethal tumor mass for a whale would be over 100 kg. A larger tumor also takes more time to develop. During this time, a large number of cell divisions and other mutations take place in the tumor. The selection of competitive phenotypes would give preference to aggressive cheaters that form a “ hypertumor ” in the actual tumor. This hypertumor would destroy the actual tumor. The larger the organism, the greater the likelihood that a hypertumor would develop. In large organisms such as whales, tumors would then be a more common occurrence, but less lethal than in small organisms.

So far, no hypothesis has been generally accepted to clarify the paradox.

literature

Individual evidence

  1. ^ R. Peto et al.: Cancer and aging in mice and men. In: Br J Cancer 32, 1975, pp. 411-426. PMID 1212409 PMC 2024769 (free full text)
  2. ^ F. Galis: Why do almost all mammals have seven cervical vertebrae? Developmental constraints, Hox genes, and cancer. In: J Exp Zool 285, 1999, pp. 19-26. PMID 10327647 (Review)
  3. ↑ F. Galis and JAJ Metz: Anti-cancer selection as a source of developmental and evolutionary constraints. In: BioEssays 23, 2003, pp. 1035-1039. PMID 14579244
  4. ↑ a b c A. M Leroi et al.: Cancer selection. ( Memento of January 6, 2009 in the Internet Archive ) In: Nat Rev Cancer 3, 2003, pp. 226-231. (Review) PMID 1261265
  5. ↑ a b c d J. D. Nagy et al: Why don't all whales have cancer? A novel hypothesis resolving Peto's paradox. In: Integrative and Comparative Biology 47, 2007, pp. 317–328. doi: 10.1093 / icb / icm062
  6. ↑ HB Andervort and TB Dunn: Occurrence of tumors in wild house mice. In: J Natl Cancer Inst 28, 1962, pp. 1153-1163. PMID 13861336
  7. ^ J. Morris and J. Dobson: Small Animal Oncology. Blackwell Science, Oxford, 2001. ISBN 0-632-05282-1
  8. ^ RJB King: Cancer Biology. 2nd edition, Pearson Education, 2000. ISBN 0-13-129454-7
  9. ^ RB Landy: Pathology of Zoo Animals. (Editors: RJ Montali and G. Migaki), Smithsonian Institution Press, 1980.
  10. ^ CJ Uys and PB Best: Pathology of lesions observed in whales flensed at Saldanha Bay, South Africa. In: J Comp Pathol 76, 1966, pp. 407-412. PMID 6008380
  11. ↑ D. Martineau et al.: Cancer in wildlife, a case study: Beluga from the St. Lawrence Estuary, Quebec, Canada. In: Environ Health Persp 110, 2000, pp. 285-292. PMID 11882480
  12. ^ S. De Guise et al.: Tumors in St. Lawrence beluga whales (Delphinapterus leucas). In: Vet Pathol 31, 1994, pp. 444-449. PMID 7941233
  13. ^ S. De Guise et al .: Possible mechanisms of action of environmental contaminants on St. Lawrence beluga whales (Delphinapterus leucas). In: Environ Health Persp 103, 1995, pp. 73-77. PMID 7556028
  14. ↑ D. Martineau et al .: Pathology and toxicology of beluga whales from the St. Lawrence Estuary, Quebec, Canada. Past, present and future. In: Sci Total Environ 154, 1994, pp. 201-215. PMID 7973607 (Review)
  15. ↑ DCG Muir et al .: Persistent organochlorines in beluga whales (Delphinapterus leucas) from the St. Lawrence River estuary. I. Concentrations and patterns of specific PCBs, chlorinated pesticides and polychlorinated dibenzo-p-dioxins and dibenzofurans. In: Environ Pollut 93, 1996, pp. 219-234. PMID 15091361
  16. ^ AV Lichtenstein: Cancer as a Programmed Death of an Organism. In: Biochemistry (Moscow) 70, 2005, pp. 1055-1064. PMID 16266279
  17. ^ AV Lichtenstein: On evolutionary origin of cancer. In: Cancer Cell Int 5, 2005, p. 5. PMID 15743536 , PMC 555547 (free full text)
  18. ^ J. Cairns: Mutation selection and the natural history of cancer. In: Nature 255, 1975, pp. 197-200. PMID 1143315
  19. ↑ JD Nagy: Competition and natural selection in a mathematical model of cancer. In: Bull Math Biol 66, 2004, pp. 663-687. PMID 15210312

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