Cancer Turnover at Old Age
To the Editor: It is often assumed that cancer incidence continues to increase with age. This was assumed recently by Campisi,[1] whose Fig. 1 shows cancer reaching 100% well before end of lifetime. Campisi then accepts that the number of senescent cells, which cannot proliferate, increases with age. To explain this paradox she has to invent a somewhat tortured explanation of the apparent paradox that senescent cells increase cancer. The recent correspondence on the Campisi paper by Kamb[2] appears to accept the idea that such an explanation is required.
However, our analysis of extensive data (a quarter of the US population) compiled by the National Cancer Institute SEER program[3] shows that cancer incidence peaks at about age 80, and appears to approach zero incidence rather than 100% (see figure below) for the oldest. Then there is no paradox and no need for a tortured explanation.
There has been some controversy historically over the quality of the cancer data for the oldest, but modern cancer registries appear to be accurate, and other investigations as well as our own work have reported this turnover in incidence.[4],[5],[6] This figure below is an analysis of more recent SEER data, which includes cancer incidence rates to older ages than previously available. The incidence turnover appears to be present for all individual cancers recorded by SEER, both male and female. Moreover, we have recently reported similar incidence turnover in a sufficiently large mice cohort for data to be statistically significant, who have been allowed to live their full natural lifetimes.[7]
We have found that the data can be fit by a beta function I(t) = (at)k-1(1-bt), where a, b, and k are constants and t is age. We derived this equation by adding the factor (1-bt) to the well known Armitage-Doll[8] multistage cancer model, and then searched for a possible biological meaning for this new factor. Cellular senescence increasing linearly with age is a plausible interpretation, since senescent cells lose proliferative ability and thus cannot cause cancer.[9] This introduction of senescence where increasing age reduces the pool of proliferating cells is similar to that of Campisi in her Fig. 4. But the data do not suggest that we have to introduce an ad hoc explanation to explain continuing cancer increases in spite of the reduction in proliferation.
We are studying whether the data still demand the extra factor when we use a mathematically exact multistage cancer model, and allow for variations in individual susceptibility.
Francesco Pompei, Ph.D.*
Ellen E. Lee
Department of Physics
*fpompei@post.harvard.edu
Age-specific incidence of all SEER cancers and the beta function I(t) = (at)k-1(1-bt) fit to the data, for males (a = 0.0076, b = 0.0092, k = 5.7) and females (a = 0.0062, b = 0.0092, k = 5.1). Error bars are ±1 SEM.