At our present state of knowledge, evidence argues that the majority of human neoplasms result from the chemical induction of neoplasia; however, it is clear that radiation, both ionizing and ultraviolet, as well as infectious agents also contribute as primary factors in the development of a significant proportion of human neoplasia. Just as with chemical carcinogenesis, in the human the basis of our knowledge of the physical and infectious causation of human cancer derives from both epidemiological and experimental findings. However, unlike many chemical carcino- gens whose carcinogenic activity in the human is based either entirely on experimental findings [e.g., 2-acetylaminofluorene, dimethylnitrosamine, and ethyleneimine (Chapter 13)] or solely on epidemiological findings [e.g., organic arsenicals and ethanol (Chapter 11)], evidence for the ultraviolet and ionizing radiation–induced human neoplasia as well as a number of viruses as causative of human neoplasia is based solidly on both experimental and epidemiological evi- dence. This chapter looks at the epidemiological evidence of physical and infectious carcinogen- esis in the human in the light of basic experimental findings, most of which have already been considered earlier in the text.
PHYSICAL CARCINOGENESIS IN HUMANS
It is likely that radiogenic neoplasms have occurred in humans sporadically since the dawn of civilization; but only in the 20th century, with the advent of our greater knowledge of the compo- nents of the electromagnetic spectrum and the existence of ionizing and ultraviolet radiation, have the cancer-inducing properties of these latter two agents been recognized. Although exper- iments in animals have shown us a great deal about the basic aspects of radiogenic neoplasia, epidemiological studies in humans have advanced our knowledge of radiogenic neoplasms to an almost equal or greater extent. The most unfortunate and at the same time the greatest single incidence of radiation-induced cancers in humans resulted from the atomic bomb explosions at Hiroshima and Nagasaki.
Ionizing Radiation Exposure
Today humans are exposed daily to both ionizing and ultraviolet radiation. Fortunately, when the sources of such radiation are recognized, exposure may often be voluntarily controlled to a much greater degree than was seen in the 1800s and early 1900s, during the days of Madame Curie,
Roentgen, radium dial painters, and the shoe-store x-ray machines. Figure 12.1 lists the common sources of exposure to ionizing radiation and the average dose per individual in millisieverts (Chapter 3) per year in this decade. As can be noted from the figure, natural sources of radiation, especially radon, a radioactive elemental gas that permeates the earth’s surface, contribute to the majority of exposure of humans to ionizing radiation. Cosmic radiation is a much smaller but significant source, while medical irradiation, both therapeutic and diagnostic, is second only to radon in its contribution to this background radiation. Sources of medical therapeutic irradiation involve relatively high doses, but these are applied to only a small segment of the total popula- tion. On the other hand, diagnostic radiation is used quite extensively in all age groups in most western and many other countries but involves much lower doses of ionizing radiation. A much smaller source of ionizing radiation also applicable to specific portions of the population (much less than 1% of total human exposure) is that of occupational exposure from nuclear power plants. That 3% of total radiation exposures come from consumer products is somewhat mis- leading (Hoel, 1995). The main sources included in this category are building materials, water supplies, and agricultural products, which are not generally thought of as consumer products. Perhaps the best known consumer product involving radiation is cigarette smoke. Polonium 210, a radioactive element, is found in tobacco as a result of airborne radon decay deposited on the tobacco plants’ leaves. However, the differences in estimates of radiation doses resulting from cigarette smoke are so disparate that the contribution of cigarette smoke to radiation carcinogen- esis is quite uncertain (cf. Hoel, 1995).
Table 12.1 shows a ranking of those cancers associated with the carcinogenic effects of ionizing radiation (Boice et al., 1996). For those cancers most frequently associated with radia- tion, one may also find other factors involved, along with the overall risk, as noted in Table 12.2. While leukemia is frequently the earliest observed radiogenic cancer after exposure to ionizing radiation of the human, such neoplasms may be considered of relatively less importance, since the radiation effect dies out in a relatively short time. However, solid tumors induced by radia- tion develop much later, and the increased cancer risk evidently persists for most if not all of the lifetime of exposed individuals (Radford, 1983).
Figure 12.1 Average annual radiation exposure: A. effective total dose equivalent in millisieverts (mSr); B. breakout of human-made exposures in mSv. (Modified from Hoel, 1995, with permission of the author and publisher.)
Table 12.1 Risk Estimates of Various Human Cancers in Relation to Exposures to Ionizing Radiation
Note: Relative risks and rankings of cancers associated with exposure to ionizing radiation in relation to the strength of the associations found and the availability of reliable estimates of radiation risk per unit organ dose.
aAssociation is inconsistently found and/or available estimates of risk are highly uncertain.
bNo reliable estimate available.
cSites for which radiation-induced cancers have not been reported or confirmed. dRetinoblastoma, Wilms’ tumor, and other tumors of embryonic origin. eMuscles, tendons, and synovial membranes of joints.
Adapted from Boice et al., 1996, with permission of the authors and publishers.
Table 12.2 Factors in Radiation Response in Three Radiogenic Cancers in the Humana