Age And Carcinogenesis

The incidence of common cancers increases with age (Figure 1). This association is universal 2 and is observed with the aging of any population around the world. A clear explanation of this phenomenon is the time-length of carcinogenesis, a stepwise process involving the activation of cellular oncogenes, and the suppression of anti-proliferative genes (anti-oncogenes)3. It is reasonable to assume that the duration of carcinogenesis reflects the number of stages involved in the pathogenesis of different tumors, and that this number be highest for tumors whose incidence peaks late in life, such as adenocarcinoma of the prostate and of the large bowel, or non-melanomatous skin cancer 3. In the era of chemoprevention and recognition and elimination of environmental carcinogens, an alternative possibility should be considered. These interventions may cause the prolongation of one or more carcinogenic steps and, in so doing; they may delay the development of cancer. For example, the incidence of lung cancer has decreased for individuals less than 60, while it has increased for older individuals 4. As a result, the peak incidence of lung cancer has become more and more delayed. Interestingly, these changes have paralleled the incidence of smoking cessation in the Western population. In this case it is reasonable to assume that the length of carcinogenesis has increased as a result of a prolongation of the late carcinogenic stages, from reduced intensity of exposure to tobacco smoke . If this hypothesis is correct, one may expect to see a progressive delay in the appearance of common cancer and an increased incidence of neoplasia in advanced ages.

Figure 1. The incidence of common cancers increases with age.

The duration of carcinogenesis may not account completely for association of cancer and aging. . The incidence of some neoplasms, such as prostate and non-melanomatous skin cancer increases more rapidly with age, than it would be expected from the time-length of carcinogenesis alone 3. These findings suggest that the concentration of cells in advanced carcinogenic stages increases with the age of an organism, enhancing the susceptibility of older individuals to environmental carcinogens 3. This possibility is supported by a host of studies of experimental carcinogenesis, summarized in another chapter of this book 3 and also by epidemiologic observations5- 9 Barbone et al reported the risk of lung cancer after exposure to an environmental pollutant in the Italian city of Trieste increased with the age of the subject at the time of exposure 6. Since 1970, the incidence of non-Hodgkin's lymphoma has increased 80% for individuals 60 and over, and that of malignant brain tumors seven fold (or 700%) for individuals 70 and older 8, 9. It is tempting to infer that older individuals develop cancer after exposure to new environmental carcinogens earlier than the younger ones, because of increased susceptibility to these substances. In other words, older subjects may represent a natural monitoring system for new carcinogens. Unfortunately this hypothesis may have proven true, at least in the case of brain tumors, as the incidence of these neoplasms is now increasing also for individuals aged 50 and older 8.

For completeness, other biological changes of aging, beside advanced carcinogenesis, may favor the development of cancer. Immune-senescence may facilitate the growth of highly immunogenic tumors 10, while proliferative senescence may result in loss of cellular apoptosis, and the production of tumor growth factors and proteolytic enzymes that promote the growth and the spreading of cancer respectively 11.

Does the incidence of cancer increase indefinitely with age? The answer to these question as become highly relevant with the progressive aging of the Western population and with the expansion of the oldest segment of the population (those 85 and older), that is increasing more rapidly than any other segment. 12. The observations of Stanta et al, who performed more than 350 autopsies of individuals aged 95 and older and in more than 100 aged 100 and older suggest that beyond a certain age the incidence of cancer might decrease 13. These authors reported that not only the incidence of cancer as cause of death and the incidence of clinical cancer, but also the incidence of occult cancer decreased after age 95. Of interest, the decline in cancer was associated with increased incidence of sarcopenia, and atrophy of multiple tissues, which suggest that at the upper extreme of age the anabolic processes are reduced to an extent that they cannot support the rapid growth of neoplastic tissues. An alternative possibility is that genes involved in longevity may also be involved in protection from cancer.

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