Cardiovascular Risks Associated With Celecoxib and Rofecoxib Dose/Drugs continued...
Dietary fiber, vegetables, and fruit
The evidence on whether dietary fiber exerts a protective role in reducing the incidence of CRC is mixed. Most animal and epidemiologic studies show a protective effect of dietary fiber on colon carcinogenesis. The term fiber is used to describe a complex mixture of compounds, including insoluble fiber (typified by wheat bran and cellulose) and soluble fiber (usually dried beans). Ingestion of fiber could modify carcinogenesis in the large bowel by a number of potential mechanisms.[110,111,112] These mechanisms include binding to bile acids, increasing fecal water and possibly diluting carcinogens, and decreasing transit time (not an obvious factor). Fiber may act as a substrate for bacterial fermentation with a resultant increase in bacterial mass and the production of short-chain fatty acids, typified by butyrate. Butyrate has been shown to have anticarcinogenic effects in vitro and is regarded as an important fuel for the colonic epithelium.[113,114] A meta-analysis of 13 case-control studies from nine countries concluded that intake of fiber-rich foods is inversely related to cancers of both the colon and rectum. The analysis did not include fiber supplements. The inverse association with fiber was observed in 12 of the 13 studies and was similar in magnitude for left-sided and right-sided colon and rectal cancers, in men and women, and in different age groups. It has been suggested that the inverse association with fiber may be reflective of some other closely associated dietary constituents, such as the anticarcinogens found in vegetables, fruits, legumes, nuts, and grains.[10,115] These substances include phenolic compounds, sulfur-containing compounds, and flavones.[116,117] In a prospective cohort study of a low-risk population, an inverse association was found with legume intake and the risk of CRC (RR for >2 times/week vs. 1 time/week = 0.53 [95% CI, 0.33–0.86; P for trend = .03]).
Other studies have corroborated the effects of dietary fiber. One study used a supplement of 10 g/day of wheat bran, cellulose, and oat bran and found a decreased mutagenic activity of fecal contents in those receiving wheat bran and cellulose supplementation, although no measurable inhibition was observed during oat bran supplementation. Fecal-total and secondary bile acid excretion increased during oat fiber supplementation.
Despite the evidence from case-control studies of a protective effect, results from the large prospective Nurses' Health Study found no difference in the risk of CRC between women in the highest quintile group compared with the lowest quintile group with respect to dietary fiber, after adjusting for age, known risk factors, and total energy intake (RR = 0.95; 95% CI, 0.73–1.25).
Many epidemiologic studies have examined the relationship between fruit and vegetable intake and the incidence of colon and/or rectal cancer, with considerable variation in findings. Perhaps the most definitive analysis to date is a prospective study that examined dietary intake data based on food frequency questionnaires from 88,764 women in the Nurses' Health Study and 47,325 men in the Health Professionals Follow-up Study. The study included a total of 1,743,645 person-years of follow-up, 937 cases of colon cancer, and 244 cases of rectal cancer. On the basis of analyses adjusted for numerous covariates, the authors found no association in women or men between overall fruit and vegetable consumption and the risk of colon or rectal cancer. Associations were not observed when the data were examined for subgroups of fruits or vegetables (with the exception of legumes, which were associated with an increased risk of colon cancer in women) or individual fruits or vegetables (with the exception of prunes, which were associated with an increased risk of colon cancer in men). Results did not change when data were examined by vitamin use status, smoking status, or family history of CRC, nor were elevated risks seen when individuals with very low levels of fruit and vegetable consumption were compared with those having the highest levels. For women and men combined, the covariate-adjusted RR of colon cancer associated with one additional serving of fruits and vegetables per day was 1.02 (95% CI, 0.98–1.05); the comparable RR for rectal cancer was 1.02 (95% CI, 0.95–1.09).