Lifestyle Interventions in the Prevention and Treatment of Cancer

Clarence H. Brown III, MD; Said M. Baidas, MD; Julio J. Hajdenberg, MD; Omar R. Kayaleh, MD; Gregory K. Pennock, MD; Nikita C. Shah, MD; Jennifer E. Tseng, MD

Disclosures

Am J Lifestyle Med. 2009;3(5):337-348. 

In This Article

Colon and Rectal Cancer

The concepts of preventing colon cancer and upper gastrointestinal malignancies through lifestyle changes have evolved over time, with inconsistent recommendations. The data obtained were derived from the multitudes of prospective and retrospective trials and reanalyzed in a meta-analytical fashion.

Because of its high incidence and its impact on human morbidity, mortality, and health dollar expenditure,[24] colon cancer prevention ranks high on the importance list of cancers to prevent. In a population, individuals also have a vested interest in preventing colon cancer because of its mostly sporadic incidence.

Dietary habits are known to contribute to or improve the risk of colon cancer,[25,26,27] and thus it would make sense to modify dietary behavior to reduce risk. In doing so, researchers have looked at intake of animal fat, red meat, fruits, vegetables, and fiber as some of the many dietary factors that may influence the risk of colon cancer.

Among the studies that have looked at the dietary content of red meat and the risk of colon cancer, a large European population study[28] looked at intake of red meat, poultry, and fish and prospectively followed the incidence of cancer. There was an increased risk of colon cancer in the group that consumed more than 180 g/d of red meat compared to those who consumed less than 20 g/d (hazard ratio of 1.35). Interestingly, the hazard ratio for high fish intake was 0.80, and the risk for poultry intake was not significantly different from that of the average population. In another case control study,[29] red meat intake was associated with a near 85% increase in colorectal cancer in individuals who ate red meat 7 times a week compared to 3 times per week. Several other studies,[30,31,32] at least one of which was a prospective,[33] have corroborated the relationship between red meat intake and colon cancer. It is not clear whether the risk is due to the heme, animal fat, or carcinogens generated during the meat preparation.[34,35] It may very well be a combination of all 3. To date, however, no studies have explored the impact of changing red meat content on colon cancer incidence. It is also unclear if the impact occurs at a young age or later in life.

Dietary fiber and the intake of fruits and vegetables have also been looked at extensively. No conclusive benefit can be drawn from the available data. A pooled analysis of 13 prospective cohort studies showed no advantage to increased dietary fiber intake when other dietary risk factors were taken into consideration.[36] Several other studies seem to corroborate these findings. Some smaller studies have shown a protective impact against colon cancer in people who consume more fruits. One large European study showed a reduction of the incidence of colon cancer when comparing the upper and lower quintile of fiber intake.[37] This benefit was limited to colon cancer but not to rectal cancer. Most of the studies evaluating the impact of dietary fiber on the incidence of adenomatous polyps showed no significant reduction in polyp formation.[38,39,40] There was, however, no disadvantage to the consumption of fruits, vegetables, and other fiber-rich foods on the incidence of colon cancer.

Dietary supplementation as a means of disease prevention is a widely used practice among the public, mainly because American Journal of Lifestyle Medicine of a perceived benefit carried down over generations of folklore. Solid data behind such practices are nearly absent, more so in the cancer prevention arena. To make evidence-based recommendations, several studies, both retrospective and prospective, have been conducted looking at the effect of such supplements on the incidence of cancer. Calcium intake in the form of dairy products has been shown to reduce the risk of colon cancer.[40,41] But high calcium levels may be associated with increased risk of prostate cancer.[42,43,44] The benefit to risk ratio has been postulated to be optimal at lower rather than higher doses, but this is subject to dispute. It may be appropriate to take into consideration the individual's risk for either cancer when deciding on calcium supplementation. The benefit from calcium occurs at high doses that are usually unattainable with regular consumption of dairy products and thus require high-dose supplements.

Vitamin D may have an effect on colonic mucosal cells[45,46] and in turn a protective effect against colon cancer.[47,48] The data are inconclusive, and in some studies, no benefit was demonstrated except in very high-dose supplementation.[49] It is important to note that the beneficial effect of sun exposure to improve vitamin D levels can be negated by the increased risk of skin cancer.[50]

Antioxidants have a very solid rationale as protective agents against the mutagenic effect of free radicals, which can affect malignant transformation,[51,52] although some investigators theorize that reactive oxygen species are part of the cellular signaling mechanisms, and thus loss of such species may also lead to malignant transformation.[53] The evaluation of several anti-oxidants, including omega-3 fatty acids, vitamin C, and vitamin E, did not conclusively demonstrate a protective effect against several cancers, including colorectal cancers.[54,55] It is also not clear if supplemental multivitamins in general offer any benefit over a well-balanced diet.[56]

Moderate to intense exercise seems to have a favorable impact on the risk of developing colon cancer. In one systematic review of published literature,[57] a definite inverse relation was observed between increased physical activity and the risk of colon cancer. A near 50% reduction in the incidence of colon cancer was observed in those undertaking the highest level of activity. This benefit was maintained even with multivariate analysis accounting for other variables such as diet and weight.[58] The benefit was evident in colon cancer more so than in rectal cancer.[59,60]

In a recent study[61] presented at the AACR 7th Annual International Conference on Frontiers in Cancer Prevention, the investigators found that, at least in women, the beneficial impact of exercise was negated by the lack of sufficient sleep. In that trial, around 6000 women were queried regarding their exercise and rest patterns. Investigators assessed the physical activity energy expenditure (PAEE) and the duration of sleep. During a 10-year follow-up, the participants were monitored for the incidence of breast and colon cancer. Of the 604 women with either breast or colon cancer, those who slept less than 7 hours per day had a higher incidence of breast and colon cancer, negating most of the beneficial effect derived from vigorous physical activity.

Exercise was also found to prevent relapse of resected stage 3 colon cancer. This was found upon analysis of the data from a large randomized trial looking at 2 different chemotherapy regimens administered in the adjuvant setting. The benefit of exercise was found to be independent of sex, body mass index, number of positive lymph nodes, age, baseline performance status, or chemotherapy received.[62] The mechanism by which physical activity and rest affect a change in malignant transformation is not clear. The effect of exercise on hormonal, immune, and weight changes may affect the inflammatory and proliferative environment that could lead to abnormal and eventually malignant cell growth. Chemoprevention, in the form of nonsteroidal anti-inflammatory agents (NSAIDs) and, more specifically, aspirin, has been shown to reduce the incidence of colonic polyps and the risk of colon cancer.[63,64,65] In several large randomized and observational trials, there was a benefit to using aspirin, but the data were not clear as to which dose was most beneficial. Some of the data implied a dose-response effect, with higher doses resulting in less incidence of polyps and malignant lesions.[66] The duration of therapy was also very important. Most of the benefit became evident after 10 years of therapy. Some population-based observational trials were analyzed after 5 years of NSAID therapy and were found to be negative.[63]

Because of the potential complications of NSAID therapy, including hemorrhagic gastritis, increased risk of bleeding, and renal complications, caution should be exercised when using these agents to prevent colon cancer and should be limited to very specific high-risk groups such as patients with familial adenomatous polyposis (FAP). When evaluating the available data, the US Preventative Services Task Force (USPSTF) concluded that the risks of using NSAIDs at the dose and for the durations required to prevent colon cancer outweigh their benefits and thus should not be used in the general population.[67]

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