Abstract
Cancer, one of the leading health concerns for humans, is by no means a human-unique malady. Accumulating evidence shows that cancer kills domestic and wild animals at a similar rate to humans and can even pose a conservation threat to certain species. Assuming that each physiologically active and proliferating cell is at risk of malignant transformation, any evolutionary increase in the number of cells (and thus body mass) will lead to a higher cancer frequency, all else being equal. However, available data fail to support the prediction that bigger animals are affected by cancer more than smaller ones. The unexpected lack of correlation between body size (and life span) and cancer risk across taxa was dubbed Peto's paradox. In this perspective, several plausible explanations of Peto's paradox are presented, with the emphasis on a largely underappreciated relation of cell size to both metabolism and cell division rates across species, which we believe are key factors underlying the paradox. We conclude that larger organisms have bigger and slowly dividing cells with lower energy turnover, all significantly reducing the risk of cancer initiation. Solving Peto's paradox will enhance our understanding the evolution of cancer and may provide new implications for cancer prevention and treatment.
Highlights
According to the last WHO report (IARC 2012), only in 2012 about 8.2 million people worldwide did die of cancers, and currently only up to 30% tumor types can be prevented
Even though the risk is extremely low for a single cell, the probability of cancer initiation will rise with increase of both life span and body size
As the rate of ROS production in a cell is a function of basal metabolic rate (BMR), organisms characterized by high BMR are subject to an increased risk of protein structure alterations, DNA mutations, and cancer (Ku et al 1993; Caulin and Maley 2011)
Summary
According to the last WHO report (IARC 2012), only in 2012 about 8.2 million people worldwide did die of cancers, and currently only up to 30% tumor types can be prevented. Long-lived, multicellular organisms should have higher probability of cancer development due to increase in the number of cell divisions (and associated errors), accumulation of toxic byproducts of cell physiology (e.g., reactive oxygen species, ROS), and prolonged negative effects of external environment (e.g., viruses, bacteria, and external toxins) (Caulin and Maley 2011; Dang 2012; Nunney 2013). As the rate of ROS production in a cell is a function of basal metabolic rate (BMR), organisms characterized by high BMR are subject to an increased risk of protein structure alterations, DNA mutations, and cancer (Ku et al 1993; Caulin and Maley 2011). The expression of DMT1 in high BMR mice was not measured, the strong positive correlation between Fe and Cd accumulation suggests that high metabolic rate contributes to increased risk of cellular toxicity and its consequences, including cancer. The overexpression of p16 in naked mole rats, in conjunction with Cdk’s inhibitor p27, seems to create a double barrier to cell proliferation and cancerogenesis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
