The Cancer Journal - Volume 9, Number 5 (September-October 1996)
Why is cancer of the elderly more benign than is cancer that occurs at younger ages?
"The wisdom of the aged body" - Zajicek, in a stimulating editoriaI in the journal (1), suggested that the fact that cancer is more frequent in the elderly could be explained if cancers in older patients were generally relatively slow growing. He pointed out that, although it is counter-intuitive to suggest that the more prevalent cancers would be slower growing, slower growth in the elderly would explain why the elderly have more tumors - there would simply be more opportunity for slow growing tumors to be present per given unit of time if they were slower growing. This hypothesis was offered as an alternative to the more usual explanation that mutations probably accumulate with time and that this accumulation accounts for the high tumor incidence in old age, but it seems evident that the two hypotheses are not mutually exclusive. Zajicek further suggested that, in accord with his hypothesis, there must be better mechanisms in the elderly to slow tumor growth -"the wisdom of the aged body".
The evidence - I am rather skeptical of the idea that the aging body has more "wisdom" in regard to cancer; by any other parameter, aging is decay- increasing incapacity - so that it strains my imsgination to think that, in this one regard, the control of the rate of tumor growth, the body reverses this universal process. Nonetheless, l think, in accord with fairly widespread opinion, that there is suggestive evidence to support the hypothesis that at least some tumor types may tend to grow more slowly in the aged. Direct evidence tends to be scarce and contradictory and what supporting data there are come, i n large part, f rom studies of breast tumors, albeit even these studies are not consistently supportive of the hypothesis (2) (3). There is a persuasive study of basal cell carcinoma (4) and ependymomas grow relatively fast in childhood (5). Many of the studies that seem to indicate a contrary phenomenon are confounded by a failure to distinguish, in laboratory studies of chemical carcinogenesis, between tumor incidence, which often tends to be high in the young, and the growth rates of the tumors. Although i am inclined to accept the hypothesis that there may indeed be a tendency for tumors to grow more slowly in the elderly, I suggest that this phenomenon need not i mp Iy a better control of tumor growth; I can and will suggest two possible mechanisms, apart from a general loss of innate vitality, that are more compatible with a loss rather than a gain of homeostatic abilities.
The first possible explanation of slower growth among tumors of the elderly stems from the observations that many and perhaps all tumors growing in the primary host are dependent to varying extents upon an immune response (6) (7). Immune reactions tend to become defective with age and consequently there may be less immune support for rapid tumor growth. Also, tumor progression to more aggressive phenotypes may also be slowed if there is less of an immune reaction (8). These considerations may be particularly pertinent in the case of breast cancer which has a markedly reduced incidence (growth rate?) in heart and kidney transplant patients (9); as already mentioned, much of the impression of slower cancer growth in the aged is probably dependent upon observations of mammary tumors.
My second explanation of the possibly slower growth of tumors in the elderly may also bear on the suggestion that there is some intimate inverse relationship between the rate of tumor growth and the tumor incidence. The argument derives from observations by Farber on the effect of chemical carcinogens in the rodent liver (10). If a near lethal dosage of a liver-carcinogen is given, a high percentage of the liver cells are killed. In scattered sites, repair results in nodules of aberrant liver tissue; these lesions are resistant, as compared to normal liver cells, to the toxic effects of the carcinogen, a phenomenon that can also be observed in many fully-developed carcinogen-induced cancers (11) (12). By virtue of these hyperplastic nodules, the animals become relatively resistant to the lethal effects of the carcinogen. Thus, this system suggests that neoplasia may be an attempt to compensate for injury to vital physiological processes. The nodules are very numerous, but usually quite benign and so reinforce the idea of a reciprocal relationship between tumor i ncidence and tumor aggressiveness.
Reaction to injury - During aging, rnany organs loose functions and neoplasia could be looked upon as an attempt at repair that occurs when more normal repair mechanisms are deficient. The more extensive the deficiencies (and the older the subject, the the more extensive the deficiencies would be) the more tumors would occur in response to the physiological signals that induce compensatory growth. In younger subjects, there would be less need of tumor as a repair mechanism, unless a strong carcinogen had been applied. Therefore, fewer tumors would arise, but those that did would be less likely to have arisen in response to a physiological imperative and thus would be less inhiblted in their growth rate by the partial restoration of the physiological deficit that tumor growth perse might provide.
In sum, l think the idea that tumors in the aged tend to be less aggressive may be true, but this could be a phenomenon dependent upon deterioration in the elderly rather than upon a new-found wisdomn,
University of Washington, 407 Lake Avenue West, Kirkland, WA 98033, USA
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