It has long been believed that older people are more cancer prone primarily because cancer-promoting gene mutations tend to accumulate slowly over time. Peter Armitage and Richard Doll famously formalized this chronological view of cancer risk in their 1953 multistage theory of carcinogenesis.1
But larger, longer-lived species don’t have commensurately outsized cancer risks, epidemiologist Richard Peto of the University of Oxford observed in the 1970s.2
Recent reports about p53 tumor suppressor gene amplification in elephant genomes suggests one possible solution to “Peto’s paradox”: larger and longer-lived species evolve stronger molecular defenses against cancer.3
But extra tumor-suppressor genes do not appear to be a general solution to cancer risk across species, notes Professor James DeGregori, PhD, of the University of Colorado School of Medicine’s molecular biology program in Aurora.
“We would argue that it can’t explain tumor suppression in animals in general,” Dr DeGregori told Cancer Therapy Advisor. What’s more, he noted, not all cancers of late adulthood require the accumulation of multiple gene mutations; chronic myeloid leukemia (CML), for example, can involve a single genomic aberration.
He and colleague Andrii Rozhok, PhD argued in a recent paper in Trends in Cancer that natural selection favoring differential investment in tissue maintenance earlier in life can explain the delay in cancer risk until post-reproductive periods.4 This is likely true “across vertebrates, and maybe all animals,” Dr DeGregori said.
Otherwise put: physiological rather than chronological aging explains increasing cancer risk in late adulthood.
Biological senescence occurs at the point in life where members of a given species experience a tipping point between the accumulating extrinsic probability of mortality from factors like starvation or predation, and declining probabilities of bearing and raising offspring. Beyond that point, natural selection’s maintenance of DNA-repair, chromosomal stability, and other molecular mechanisms of cellular integrity and coordination wanes, and organisms become prone to senescence, and to cancer.
Natural selection invests in the body’s somatic integrity just long enough to “get a return on its investment, in terms of reproductive success,” Dr DeGregori explained.