This map of the world shows the rates of cancer increasing (red arrows) or decreasing (blue arrows) when specific populations move from one location to another. Such observations suggest the importance of environmental factors, including diet, in dictating cancer risk. (B) Some estimated effects of environment and lifestyle on cancer in the United States (US). The table shows both the yearly deaths in the US attributable to each cancer and the estimated percentage of that cancer that could be eliminated through prevention. (B, data from G.A. Colditz, K.Y. Wolin and
S.
Gehlert, Sci. Transl. Med. 4:127rv4, 2012.) of aromatic hydrocarbons and derivatives of them such as aromatic amines, nitrosamines, and alkylating agents such as mustard gas. Although these chemical carcinogens are diverse in structure, a large proportion of them have at least one shared property—they cause mutations. In one common test for mutagenicity (the Ames test), the carcinogen is mixed with an activating extract prepared from rat liver cells (to mimic the biochemical processing that occurs in an intact animal). The mixture is then added to a culture of specially designed test bacteria and the bacterial mutation rate measured. Most of the compounds scored as mutagenic by this rapid and convenient assay in bacteria also cause mutations or chromosome aberrations when tested on mammalian cells.
A few of these carcinogens act directly on DNA. But generally the more potent ones are relatively inert chemically; these chemicals become damaging only after they have been converted to a more reactive molecule by metabolic processes in the liver, catalyzed by a set of intracellular enzymes known as the cytochrome P-450 oxidases. These enzymes normally help to convert ingested toxins into harmless and easily excreted compounds. Unhappily, their activity on certain chemicals generates products that are highly mutagenic. Examples of carcinogens activated in this way include benzo[a]pyrene, a cancer-causing chemical present in coal tar and tobacco smoke and the fungal toxin aflatoxin B1 (Figure 20–38).
Fifty Percent of Cancers Could Be Prevented by Changes in Lifestyle
Tobacco smoke is the most important carcinogen in the world today. Even though many other chemical carcinogens have been identified, none of these appear to be responsible for anything like the same numbers of human cancer deaths. It is sometimes thought that the main environmental causes of cancer are the products of a highly industrialized way of life—the rise in pollution, the enhanced use of food additives, and so on—but there is little evidence to support this view. The idea may have come in part from the identification of some highly carcinogenic materials used in industry, such as 2-naphthylamine and asbestos. Except for the increase in cancers caused by smoking, however, age-adjusted death rates for most common human cancers have stayed much the same over the past half-century, or, in some cases, have declined significantly (Figure 20–39). Survival rates, moreover, have improved. Thirty years ago, less than 50% of patients lived more than five years from the time of diagnosis; now, more than two-thirds do so.
(A) AFLATOXIN AFLATOXIN-2,3-EPOXIDE CARCINOGEN BOUND TO GUANINE IN DNA
Figure 20–38 Some known carcinogens. (A) Carcinogen activation.  A metabolic transformation must activate many chemical carcinogens before they will cause mutations by reacting with DNA. The compound illustrated here is aflatoxin B1, a toxin from a mold (Aspergillus flavus oryzae) that grows on grain and peanuts when they are stored under humid tropical conditions. Aflatoxin is an important cause of liver cancer in the tropics. (B) Different carcinogens cause different types of cancer. (B, data from Cancer and the Environment: Gene Environment Interactions, National Academies Press, 2002.)