Peto's Paradox: evolution's prescription for cancer prevention Peto's Paradox: evolution's prescription for cancer prevention
Paper summary There is no correlation between body size and cancer incidence across animal species. From a logical point of view such a correlation would be expected. If one assumes that each proliferating cell in an individual multicellular organism has an equal probability of acquiring a cancerous mutation, then organisms with significantly more cells should have a higher probability of developing a cancerous tumour. This is known as Peto's paradox. This paper puts Peto's paradox in the context of an evolutionary strategy to allow large multicellular organisms to live beyond reproductive age. Evolutionary theory describes the genetic instabilities (and variations) leading to the development of tumour suppression mechanisms. The evolutionary rules are clearly stated in box 1 and are reasonable considering the known heterogeneity of tumours. I particularly like this paper because it puts some captivating numbers on the effect of tumour suppression in some animals. It takes one extreme of animal size, and a well known character in terms of tumour suppression, the blue whale, and makes back of the envelope calculations to what its cancer incidence should theoretically be. Given that the blue whale is 1000 times the size of a human the authors predict that all blue whales should have colorectal cancer by the age of 80. For information, blue whales can live to more than 100 years. Within a species size is related to cancer risk (Hooray I knew there would be some advantage to being only 165cm) whereby a 3-4 mm increase above the average leg length results in an 80% higher risk of non smoking related cancers. All this suggests that large organisms (that also happen to live longer) have acquired mechanism to suppress cancer. The authors describe such cancer suppression mechanisms including lower somatic mutation rates, different tissue architecture, redundancy in tumour suppressor genes and a somehow lower selective advantage of mutant cells and increased sensitivity to contact exhibition to name but a few. A particularly tantalising theory suggested by Nagy et al is that of "hypertumours" whereby a parasitic growth from the cancerous tumour results in a lowering of the overall fitness tumour fitness. This hypothesis has yet to be tested. My understanding is that comparing cancer suppression mechanisms across the species will lead to a better understanding of the evolutionary process involved in cancer progression and perhaps will reveal knowledge to help better develop strategies for cancer therapies in humans.
Peto's Paradox: evolution's prescription for cancer prevention
Aleah F. Caulin and Carlo C. Maley
Trends in Ecology & Evolution - 2011 via CrossRef

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