investigation. Lashner (1993) subsequently compared prospectively the erythrocyte folate concentrations in patients with neoplastic changes in the colorectum with those for disease-matched control patients without neoplasia. The mean erythrocyte concentration was significantly lower in the individuals with neoplasia (988 nmol/L [454 ng/mL]) than in the control patients (1,132 nmol/L [520 ng/ mL]) but was still well within the normal range, which is in line with observations of erythrocyte folate concentrations and dysplasia in the uterine cervix (Butterworth et al., 1992a). Meenan and colleagues (1996) described the lack of association between erythrocyte folate levels and colonic biopsy specimens in healthy individuals, indicating the potential difficulty in predicting localized folate deficiency. In a subsequent report (Meenan et al., 1997), epithelial cell folate depletion occurred in neoplastic but not adjacent normal colonic mucosa.
In general, epidemiological studies support an inverse relationship between folate status and the rate of colorectal neoplasia (Mason and Levesque, 1996). Two large, well-controlled prospective studies support the inverse association between folate intake and incidence of colorectal adenomatous polyps (Giovannucci et al., 1993) and colorectal cancers (Giovannucci et al., 1995). In these two studies, moderate-to-high alcohol intake greatly increased the neoplastic risk of a low-folate diet. There was a significant 35 percent lower risk of adenoma in those in the highest quintile of folate intake (approximately 800 µg/day) relative to those in the lowest quintile (approximately 200 µg/day, relative risk approximately 0.65). The adverse effect of high alcohol intake coupled with a low-folate diet was confirmed by Glynn and colleagues (1996), who observed a significant fourfold increase in risk of colorectal cancer. Physicians’ Health Study participants with the MTHFR polymorphism had reduced risk of colon cancer, but low folate intake or high alcohol consumption appeared to negate some of the protective effect (Ma et al., 1997) (see Appendix L for further discussion of MTHFR polymorphism).
More evidence for or against a causal relationship between folate status and colorectal cancer will be provided by data from prospective controlled intervention trials that are currently under way.
As reviewed by Mason and Levesque (1996), data are not sufficient for making conclusions regarding the possible role of folate in reducing the risk of cancer of the lung, esophagus, or stomach.