Diet and cancer prevention in humans: review of the evidence and its application to companion animals
Authors: Kristal A. R. 
Published: March 2008

What is cancer?
Cancer is disease of damaged DNA. DNA in every cell is under constant attack, from by‐products of normal metabolism as well as external factors such as radiation and carcinogens. Humans have evolved complex mechanisms to protect DNA from damage so that affected cells either repair their DNA or die. But under certain conditions, cells with damaged DNA can both survive and gain a growth advantage over surrounding cells. Over many years, these rapidly‐growing cells can accumulate additional DNA damage (called somatic mutations) and eventually, when the damage is quite severe, they can become cancers. There are three abnormal characteristics that cells must acquire to become cancers: (1) independence from normal controls on cell growth (proliferation) and death (apoptosis); (2) the ability to stimulate formation of blood vessels to provide nutrients to support rapid cell growth (angiogenesis); and (3) the ability to grow beyond their normal location first locally (invasion) and eventually in distant sites (metastasis). Although these characteristics are shared by all cancers, the clinical characteristics of cancer vary enormously. Some cancers, for example low‐grade prostate cancer, are very slow growing and take decades to become metastatic; other cancers, such as pancreas cancer, are highly invasive and uniformly and rapidly fatal.

How could diet affect cancer?
The two key components underlying the development of cancer are damage to DNA and rapid cell proliferation. Many mechanisms that protect DNA from damage are dependent upon dietary intake of antioxidants or are regulated by bioactive compounds found in foods. Cell growth is regulated by many factors, including steroid hormones and growth factors such as the insulin‐like growth factors. Cell growth is also influenced by inflammatory cytokines, which stimulate the replacement of cells damaged by inflammatory reactions. Dietary patterns and diet‐related factors such as obesity affect both the levels of circulating hormones and growth factors, and the levels of pro‐ and anti‐inflammatory cytokines. In laboratory experiments, based on cell cultures and animal models, we can consistently show that bioactive food compounds and dietary manipulation can affect DNA damage and cell growth, and that these effects mediate the development and/or growth of cancer cells. Thus, most scientists believe that diet has an important influence on the risk of developing cancer.

What is the evidence that diet affects cancer risk? The strongest evidence that diet affects cancer risk in humans is from comparisons across countries. In these studies, there are strong associations between “food disappearance,” (total food production and imports minus food used as animal feed) and cancer incidence, for example between dietary fat and breast cancer. From these studies we have estimated that about 35% of all cancers are associated with diet. However, more analytically rigorous approaches to examining diet and cancer relationships, such as epidemiological studies and large randomized clinical trials, have not yielded consistent and clear answers. This has been very frustrating to scientists working in the field, and has challenged us to examine both our hypotheses about diet and cancer and the approaches we use to study diet and cancer. We now understand that cancer is a very complex disease which is affected strongly both by an individual's genetic characteristics and their life‐long environmental exposures. We have learned that the standard methods used to measure diet in large epidemiological studies are probably not sufficiently accurate to detect moderate diet/cancer associations. And we have learned that randomized clinical trials to test effects of dietary change or dietary supplements on cancer risk can fail to detect associations. Thus, the entire field is now in flux as the next generation of studies are being designed.

What specific diet and diet‐related factors affect cancer risk? Currently, the best evidence that diet affects cancer risk is based on the well‐established associations of obesity with increased cancer incidence and mortality. Obesity increases the risk of cancer mortality by about 30‐50%, but this association is remarkably different across cancers. Obesity appears to have an effect both on the risk of developing cancer and on the risk of dying from cancer after diagnosis and treatment. Alcohol is a direct irritant which, in combination with smoking, causes oral and esophageal cancer. Alcohol also increases the risk of breast cancer by interfering with folate metabolism, and it increases the risk of liver cancer through the inflammatory response to cirrhosis. Other dietary factors for which we have strong evidence are fat, selenium, and vegetables, especially cruciferous vegetables. Studies examining antioxidant intake from either foods or supplements have been most often negative, suggesting that in humans the role of dietary antioxidants and cancer is much more complex than in animal models. Finally, there are a long list of foods and food components that have been picked up by the media and food manufacturers as ‘cancer prevention agents,’ most notably lycopene (tomatoes), resveratrol (red wine), and genistein (soy), however most of these have not stood up to scientific scrutiny.

Does studies in humans obtain for domestic animals? The applicability of studies on cancer risk in humans to domestic, companion animals is uncertain. Some mechanisms linking diet and diet‐related factors with cancer, for example the associations of obesity with serum steroids and inflammatory cytokines, the importance of selenium for the antioxidant activity of selenoproteins, and the function of vitamin E as an antioxidant, are likely similar between humans and domestic animals. In contrast, the types, distributions and activity of xenobiotic enzymes differ across species; thus the dietary induction of enzyme activity, the prevalence and types of genetic polymorphisms, and the relative susceptibility to carcinogens will likely differ as well. Finally, requirements for nutrients differ across species, with the most obvious being the requirement of dietary vitamin C that is exclusive to humans and guinea pigs. The very limited research on diet and cancer in dogs suggests that obesity, especially when young, and exposure to table foods increase breast cancer risk, while the relationship of obesity with cancer overall are probably as complex as those seen in humans. Rigorous studies to understand the association of diet with cancer risk in domestic, companion animals will be difficult, primarily because the costs of this research are high.