If either chance or
environmental exposure was the dominant carcinogen, cancer risk would increase continuously with
age, but it doesn’t. For all cancers studied, risk exhibits three phases: 1)
Low risk at young ages, followed by 2) an increase in risk to a maximum at some
later age, followed by 3) a plateau or decline in risk at advanced ages. Only a
genetically-determined discontinuous process can explain this pattern. We
analyzed differences in risk between tissues of tumor origin and between
geographic locations, genders, races, and ethnicities for clues. Our analyses
suggest that normal tissue differentiation is safe, but inadequate. At some
critical age, regeneration or dedifferentiation is required and this is an
invitation to carcinogenesis. Upon reaching this critical age, risk varies with
the size of a target, which may correspond to the number of regenerating or
dedifferentiating stem cells. Cancer incidence rates were analyzed for melanoma
and cancers of the mouth, esophagus, stomach, small intestine, colon, rectum,
liver, pancreas, larynx, bronchus, breast, and kidney in populations
distributed worldwide and within the United States in two time eras. Over all
cancers, in all populations, and both eras, the difference in age-specific
rates between ages 50 and 40, d50-40, correlated strongly with
age-standardized rates. Differences in d50-40
correlated strongly with differences in age-standardized rates between genders,
races, and ethnicities. We suggest that, for the cancers studied, the critical
age occurs between 40 and 50. If environmental exposure or segregating genes was the dominant carcinogen,
the rank order of cancer risk between tissues of tumor origin would vary from
one geographic location to another, because environment and segregating genes
vary between geographic locations. Such variation was observed between rank
order in Japan and rank order in other countries, but not between rank orders
in the other countries. We suspect, therefore, that environment or segregating
genes play an important role in determining the difference in rank order of
risk for the tissues of tumor origin between Japan and other countries. If
chance or environmental exposure was the dominant carcinogen, cancer risk would correlate strongly between
pairs of cancers across populations, but it doesn’t. Coefficients of risk
between pairs of cancers are, typically, moderate at best. Only mouth, larynx,
bronchus, and kidney show strong coefficients. By our measures, cancer risk
from aging exceeds cancer risk from other-than-aging causes in all populations
in both eras. We suspect that the aging risk is determined by genes that are
common to all members of our species, and we suggest that inhibiting tissue
injury and unnecessary growth will reduce cancer risk.
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