Page 268 - 20dynamics of cancer

STEM CELLS: TISSUE RENEWAL 253

Table 12.1 Cancer incidence in Denmark, 1943–1967

Type Commonest sites Total cases %
Carcinomas
External epithelia Skin, large intestine,
lung, stomach, cervix 168,591 56
Internal epithelia Breast, prostate, ovary,
bladder, pancreas 110,182 36
Sarcomas and leukemias 23,801 8
From Cairns (1975), based on data from the Danish Cancer Registry (Clemme-
sen 1964, 1969, 1974).

RENEWING TISSUES AND EPITHELIAL RISK
The epithelium of the human colon turns over at least once per week
throughout life. As cells die at the surface, they are replaced by new cell
divisions. By age 60, a person has been through at least 3,000 replace-
ment cycles, which means that some cell lineages must pass through
many generations. Those renewing lineages would be at high risk for
accumulating mutations and progressing to cancer.
Cairns (1975) recognized the importance of tissue renewal in the dis-
tribution of cell divisions, and the key role that cell division plays in
cancer progression. He wrote:
We may ... expect to find, especially in animals which undergo
continual cell multiplication during their adult life, the evolution
of mechanisms that protect the animal from being taken over by
any “fitter” cells arising spontaneously during its lifetime—that is
mechanisms for minimising the rate of production of variant cells
and for preventing free competition between cells ... Because most
of the cell division is occurring in epithelia, that is where we may
expect to find the protective mechanisms most highly developed.

12.2 Stem-Transit Program of Renewal

Cairns (1975) suggested various mechanisms that protect against the
accumulation of somatic mutations and the competition between cell
lineages.
One protective mechanism arises from the distinction between stem
cells and transit cells. The long-lived stem cells renew the tissue over