While the data in Table 11.3 are necessarily incomplete in their coverage of the literature, certain trends are clearly evident. Excess dietary meat—especially cooked meat, dietary fat, and excess dietary calories have been associated in a number of studies with an increased risk of a variety of human neoplasms. On the other hand, average increased intake of fruits and vegetables, as well as a number of the micronutrients found in these substances—e.g., vitamins A, C, E, and other carotenoids—are associated with a decreased risk of developing a variety of neoplasms in the human, especially when taken at somewhat increased levels compared with average consump- tion. Unique dietary factors include the possible effect of dietary cholesterol in increasing the risk of esophageal, lung, and pancreatic cancer and the effect of dietary salt on the development of stomach, nasopharyngeal, and esophageal cancer.
Other dietary constituents that have been studied in relation to the risk of human cancer include milk and dairy products, studies that have been inconclusive for ovarian cancer risk (Mettlin and Piver, 1990; Cramer et al., 1989) but have suggested a relation to an increased risk of lymphoid neoplasia in at least one investigation (Ursin et al., 1990). More theoretical (Parodi, 1997) and experimental studies ( Papenburg et al.,1990) have suggested that milk components may inhibit the development of neoplasia in humans and animals. Soy protein and its associated constituents, which make up major components of the human diet in certain parts of the world, especially southeast Asia, have been suggested as preventive for human cancer development (Persky and van Horn, 1995; Barnes, 1998), whereas animal studies, although predominantly supportive of these epidemiological indications, are by no means consistent (Messina et al., 1994; Sørensen et al., 1998). A more consistent inhibition of neoplasia in human and animals can be seen with the family of cruciferous vegetables. These include such common vegetables as horseradish, turnip, cabbage, brussels sprouts, cauliflower, broccoli, Chinese cabbage, radish, and mustard (cf. Verhagen et al., 1997). A number of epide- miological and animal studies have shown the effectiveness of cruciferous vegetables in inhibit- ing the development of a variety of human and animal neoplasms (cf. Nestle, 1997). The principal active ingredients in the inhibition of carcinogenesis are the glucosinolates and their hydrolysis products. These share a common basic skeleton containing a β-D-thioglucose group- ing, a side chain, and a sulfonated oxime moiety but differ in their side chain. A general structure is as follows:
These agents are active inducers of phase II xenobiotic metabolizing enzymes (Chapter 3). In addition, they are effective in preventing oxidative DNA damage both in humans (Verhagen et al., 1997) and in rodents (Deng et al., 1998). Another chemical commonly found in cruciferous vegetables, indole-3-carbinol, also inhibits experimental carcinogenesis, probably by a similar mechanism (Grubbs et al., 1995), but in some studies clear evidence for tumor-promoting activ- ity of carcinogenesis by this compound has also been found (Dashwood, 1998). Thus, there is ample evidence to indicate the importance of a variety of dietary plants and their constituents in effectively inhibiting the development of neoplasia in mammalian organisms. It should be noted that such inhibition occurs predominantly at the stage of tumor promotion, as noted from the listing seen in Table 11.4. While the listing of types of neoplasia affected by these dietary factors is incomplete, as noted from Table 11.3, the neoplasms listed represent numerically the pre- dominance of human neoplasia affected. Thus, as expected and readily noted from Table 11.3, preventing the dietary induction of human neoplasia by appropriate alternate dietary intake is not only feasible but, in most countries, readily or reasonably applicable. A number of studies have actually attempted to estimate the preventive potential of dietary alteration in the inci- dence of specific human neoplasms (cf. Miller et al., 1994). Table 11.5 summarizes a number of studies attempting to estimate potential preventive effects of dietary alterations on various neoplasms.
Thus, while one may be unwilling to accept the suggestion that 35% of human cancer is directly related to diet (Doll, 1992), there is increasing evidence that diet and related factors play
Table 11.4 Stages of Carcinogenesis at Which Dietary Factors Alter Cancer Incidence (Humans)
Table 11.5 Estimates of Potential Effects of Dietary Change on the Incidence of Various Cancers
aPAR, population-attributable risk. Square brackets are used when some of the benefit derives from eliminating smok- ing. Estimates for males, except for breast, endometrium, and ovarian cancer. ? signifies that no estimate of effect is available.
Modified from Miller et al., 1994, with permission of authors and publisher.
a major role in the incidence of human cancer. However, this role is quite complex and in all likelihood does not result from the direct conversion of normal to neoplastic cells by dietary constituents but rather stems from an alteration in the development of cells within the organism that have the potential for neoplastic growth.