Cell size, body size and Peto's paradox.

Carcinogenesis is one of the leading health concerns afflicting presumably every single animal species, including humans. Currently, cancer research expands considerably beyond medicine, becoming a focus in other branches of natural science. Accumulating evidence suggests that a proportional scale of tumor deaths involves domestic and wild animals and poses economical or conservation threats to many species. Therefore, understanding the genetic and physiological mechanisms of cancer initiation and its progression is essential for our future action and contingent prevention. From this perspective, I used an evolutionary-based approach to re-evaluate the baseline for debate around Peto's paradox. First, I review the background of information on which current understanding of Peto's paradox and evolutionary concept of carcinogenesis have been founded. The weak points and limitations of theoretical modeling or indirect reasoning in studies based on intraspecific, comparative studies of carcinogenesis are highlighted. This is then followed by detail discussion of an effect of the body mass in cancer research and the importance of cell size in consideration of body architecture; also, I note to the ambiguity around cell size invariance hypothesis and hard data for variability of cell size across species are provided. Finally, I point to the new research area that is driving concepts to identify exact molecular mechanisms promoting the process of tumorigenesis, which in turn may provide a proximate explanation of Peto's paradox. The novelty of the approach proposed therein lies in intraspecies testing of the effect of differentiation of cell size/number on the probability of carcinogenesis while controlling for the confounding effect of body mass/size.