Effect of Diet
An unhealthy diet could account for up to 30% of all cancers in developing countriesand perhaps 35% of cancer deaths in the United States. Hence, along with tobacco use, diet is one of the most important modifiable risk factors for cancer. Given the diverse and complex nature of the human diet, however, it is also one of the most difficult factors to study in large human populations. Numerous instruments for dietary assessment have been developed and validated.As in physical activity assessment, the choice of instrument depends largely on the intended purpose. A vast body of epidemiologic research has addressed a wide array of research questions related to cancer and diet in an attempt to disentangle individual dietary effects. Here we highlight some of the strongest associations identified thus far,although more associations will undoubtedly emerge in the future.
Sugar, Fast Foods, and Other Energy-Dense Foods
High-calorie foods and drinks are suspected risk factors for cancer given their contributions to weight gain, overweight, and obesity. The risks deriving from specific aspects of an energy-dense diet, however, are not as clear. Foods containing high amounts of sugar, for example, may be associated with increased colorectal cancer risk, and biologic mechanisms have been proposed, but the overall evidence in humans is currently limited and merely suggestive.
In terms of fat intake, evidence from a substantial number of human studies has provided only limited, but suggestive evidence for increased risk of cancers of the lung, breast, colorectum,and possibly prostate.Despite plausible biologic mechanisms for these cancers, the overall findings surrounding fat intake and cancer incidence are inconsistent. Notably, dietary fat has been studied in relation to breast cancer recurrence and survival in two large randomized controlled trials. Findings from the Women’s Intervention Nutrition Studyand the Women’s Healthy Eating and Living studyhave suggested limited prognostic gain from lowering dietary fat, although there may be some decrease in recurrence rates for certain subgroups
of postmenopausal women. More limited evidence suggests that the aggressiveness of prostate tumors and deaths from prostate cancer may be related to higher total and saturated fat intakes.
Fruits and Vegetables
A plant-based diet rich in fruits, vegetables, and whole grains is continually recommended for the prevention of various cancers.In a comprehensive review of published literature on this subject, a variety of fruits and vegetables appeared likely to preventcancer, although the evidence was not fully convincing (see table 3.3).
Compared to cancer incidence, far fewer studies have examined fruit and vegetable intake in relation to cancer prognosis. Very limited data support a decreased risk of recurrence or progression of prostate cancer, for example, with higher intake of tomatoes or lycopene.Vegetable intake has been linked to longer survival from ovarian cancerand advanced lung cancer,but again, these findings are very preliminary. The effects on breast cancer prognosis are also unclear.In the Women’s Healthy Eating and Living randomized controlled trial of breast cancer patients, long-term adoption of a low-fat diet high in fruits, vegetables, and fiber had no effect on breast cancer recurrence or survival.
Fruits and vegetables could prevent cancer through multiple, interrelated mechanisms. Promotion of a healthy body weight, prevention of oxidative stress and DNA damage, and the ability to alter the activities of carcinogen-activating enzymes are just a few possible mediating pathways to prevention. Higher intake may also favorably alter immune function, inflammation, and cellular growth.
According to one international report on cancer prevention,a diet high in fiber may well reduce the risk of colorectal cancer. Yet, at least one pooled analysis of research on this subject found no effect from fiber beyond the effects of other dietary risk factors.Part of the difficulty in studying fiber intake in humans may be that intake is too low to observe any benefit.The Polyp Prevention Trial, conducted in the United States, explored the effect of increasing dietary fiber intake over four years (and also lowering fat and increasing fruit and vegetable intakes) in people who had previously experienced one or more colorectal adenomas. Adenoma recurrence was significantly lowered among the most compliant study participants,implying that a high-fiber diet may also lower the risk of colorectal cancer recurrences.
The reasons that fiber may be protective are unclear, but several mechanisms have been proposed.High fiber intake favorably alters the quality of the feces by diluting its contents, increasing its weight, and shortening transit time through the colon. The outcome of these effects is decreased contact between potential fecal carcinogens and colonic cells. As well, fiber fermentation products (e.g., butyrate) produced in the gut can help promote healthy cellular growth. Furthermore, intakes of fiber and folate are correlated, and hence, the observed effects may actually be from folate.
Red Meat and Processed Meat
There is convincing evidence that consumption of red meat and processed meat (i.e., preserved by smoking, curing, salting, or with preservatives) increases the risk of colorectal cancer.Very few studies, however, have examined the effect of diet on colorectal cancer recurrence and survivorship. In one follow-up study of patients with stage III colon cancer, postdiagnosis intake of a “Western diet” (high intake of red and processed meats, sweets, French fries, and refined grains) was associated with higher risks of recurrence and death, whereas a “prudent diet” (fruits, vegetables, legumes, fish, poultry, and whole grains) was not associated with an increased risk.Whether these findings are attributable to meat intake specifically, however, is unknown.
Red and processed meats might increase cancer risk because potentially carcinogenic N-nitroso compounds are formed in the stomach and gut following their ingestion. Cooking at high temperatures produces potentially carcinogenic by-products, and the heme iron content of meats may also promote DNA damage and cancer in the colon. Moreover, processed meats are high in salt, which also encourages the formation of N-nitroso compounds. In addition, higher meat consumption may coincide with low intakes of fruits, vegetables, and fiber, which may decrease cancer risk.
There is now a wealth of convincing evidencethat total alcohol intake, irrespective of the source, increases the risk of cancers of the mouth, pharynx, larynx, esophagus, colorectum (in men)and breast in both pre- and postmenopausal women.With respect to breast cancer, the increased risk from alcohol appears to be the most elevated in women with low folate intake.It is less convincing, but still probable, that alcohol consumption increases the risk of liver cancer and of colorectal cancer in women. Alcohol in small quantities does not appear to prevent cancer as it does cardiovascular disease.The effect of alcohol intake on cancer prognosis has been studied in relation to breast cancer; however, the effect remains uncertain. Alcohol intake has not been associated with breast cancer recurrence or overall survival in most studies of women diagnosed with breast cancer.
Alcohol may increase cancer risk via multiple pathways.Some of its metabolites and by-
products, for example, may be carcinogenic. Alcohol also acts as a solvent, which facilitates the entry of other cancer-causing compounds (e.g., as found in tobacco) into cells. Hence, for certain cancers, the combined cancer-causing effects of alcohol and tobacco are worse than they would be for either substance alone. Furthermore, alcohol may indirectly alter normal cell cycles, affect the metabolism of other carcinogens, increase circulating hormone levels, and reduce folate levels.
Total salt intake and the intake of salted and salty foods are probably associated with stomach cancer, and intake of Cantonese-style salted fish appears to increase the risk of nasopharyngeal cancer.Salt intake could plausibly cause stomach cancer by damaging the stomach lining, increasing the formation of N-nitroso compounds, which are potentially carcinogenic, or interacting with other carcinogens. It is also hypothesized that salt intake and Heliobacter pylori infection might act synergistically to increase risk. Salted fish may increase the risk of cancer of the nasopharynx because of its N-nitrosamine content.
In their report on diet and cancer prevention, the World Cancer Research Fund and the American Institute for Cancer Researchdo not recommend dietary supplements for the purpose of preventing cancer. Instead, they recommend that proper nutrition be attained through the intake of foods alone. Although evidence suggests that some supplement use may help prevent cancer, high doses can actually causecancer in certain subgroups of the population. For example, convincing evidence supports a causal role for high-dose beta-carotene supplement use in lung cancer, depending on smoking status and genetics.The American Cancer Society similarly advises cancer survivors to avoid very high doses of vitamins, minerals, and other dietary supplements; they state that although low doses may be useful, they should only be taken with advice from a health care provider.