Peto's Paradox: Why Are Larger, Longer-Lived Animals Less Likely to Develop Cancer?

Cancer cells arise when normal cells accumulate errors in DNA replication across many generations of cell division. As these mutations continue to accumulate, the DNA of descendant cells gradually diverges from that of the original healthy cell lineage. This divergence disrupts normal cellular function and leads to abnormal physiological behavior. Within the body, such cells become harmful. If they continue to proliferate, they may initially disrupt the function of a local tissue, and in more severe cases they may metastasize throughout the body, ultimately impairing vital physiological functions and leading to the death of the organism.

Fortunately, organisms possess tumor suppressor genes—such as TP53 and Rb—as well as immune surveillance mechanisms that eliminate the vast majority of potentially tumor-forming cells. Under this framework, it was traditionally assumed that larger animals should face a higher risk of cancer. After all, larger bodies contain more cells, and longer lifespans imply more rounds of cell division. Both factors should theoretically increase the likelihood of carcinogenic mutations.

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