title: Peto's paradox and human cancers.
abstract: Peto's paradox is the lack of the expected trend in cancer incidence as a function of body size and lifespan across species. The leading hypothesis to explain this pattern is natural selection for differential cancer prevention in larger, longer lived species. We evaluate whether a similar effect exists within species, specifically humans. We begin by reanalysing a recently published dataset to separate the effects of stem cell number and replication rate, and show that each has an independent effect on cancer risk. When considering the lifetime number of stem cell divisions in an extended dataset, and removing cases associated with other diseases or carcinogens, we find that lifetime cancer risk per tissue saturates at approximately 0.3-1.3% for the types considered. We further demonstrate that grouping by anatomical site explains most of the remaining variation. Our results indicate that cancer risk depends not only on the number of stem cell divisions but varies enormously (approx. 10 000 times) depending on anatomical site. We conclude that variation in risk of human cancer types is analogous to the paradoxical lack of variation in cancer incidence among animal species and may likewise be understood as a result of evolution by natural selection.
authors.affiliation: Institut des Sciences de l'Evolution, Université de Montpellier, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Noble
authors.affiliation: Institut des Sciences de l'Evolution, Université de Montpellier, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kaltz
authors.affiliation: Institut des Sciences de l'Evolution, Université de Montpellier, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA michael.hochberg@univ-montp2.fr.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hochberg
mesh_terms: D005075:Biological Evolution; D002452:Cell Count; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology* / Q000473:pathology; D009929:Organ Size; D012307:Risk Factors; D013234:Stem Cells / Q000473:pathology
keywords: Peto's paradox; cancer; carcinogenesis; disease; stem cells; ‘bad luck’ mutations