peto's paradox

why cancer persists

limits of natural selection
antagonistic pleiotropy

why cancer persists - limits of natural selection

selection is weak after organisms reach reproductive age
selection shadow means that events later in life are harder for natural selection to filter out

why cancer persists - antagonistic pleiotropy

mutations that increase fertility may increase cancer risk as well
e.g. Xmrk gene in swordfish produces melanin spots which increases melanoma risk but is beneficial in reproductive success

short lifespan animals

fast reproduction
decreased survival
increased offspring
decreased somatic maintenance
increased cancer incidence

long lifespan animals

slow reproduction
increased survival
decreased offspring
increased somatic maintenance
increased DNA damage sensitivity and repair

peto’s paradox

larger organisms have more cells and should have increased cancer incidence but don’t

hypotheses for peto’s paradox

enhanced cancer resistance
hypertumours
superior DNA repair

enhanced cancer resistance

elephants have 5% lifetime cancer risk
40 TP53 copies - increased apoptotic rate in response to DNA damage

superior DNA repair - study

comparison of mutation rates in intestinal crypts of animals
laser microdissection - isolation of single cells
found linear rate of mutation increase over age in all species
inverse correlation of mutation rate with lifespan

evidence for improved DNA repair in bowhead whale

CIRBP mutations sequenced - involved in cell cycle
found to improve DNA repair in human cell lines

cancer resistance in naked mole rat

strong contact inhibition in fibroblasts
activated by p16
pALT CDK inhibitor produced by alternative splicing and is activated in ECI
high abundance of HMM-HA initiates ECI and protects cells from ROS

cancer resistance in bats

resistant telomeres
miRNA tumour suppressors
robust DNA repair mechanisms