The use of folic acid antagonists and the risk of colorectal cancer.

PURPOSE: Since folate is associated with a reduced risk of colorectal cancer, we hypothesized that folic acid antagonists might increase the risk. We used data from a population-based case control study of medication use and colorectal cancer to evaluate the hypothesis.

METHODS

Case patients with adenocarcinoma of the colon or rectum were ascertained from participating hospitals in Massachusetts and the Massachusetts cancer registry (MCR) from January 1, 2001, through November 30, 2004. Age-, sex-, and precinct-matched control subjects were chosen from Massachusetts town lists. Information on folic acid antagonist use and other relevant data were obtained from 1809 cases and 1809 matched controls by telephone interview and by a self-administered dietary questionnaire. We used logistic regression models to estimate odds ratios among 1229 case patients and 1165 control subjects who provided satisfactory dietary information and did not have Crohn's disease or ulcerative colitis.

RESULTS

The odds ratio for colorectal cancer among regular users of folate-containing supplements was 0.7 (95%CI 0.6-0.9). The odds ratio for regular use of folic acid antagonists was 1.3 (95%CI 0.9-1.9). Contrary to expectation, the odds ratio was reduced in the highest category of alcohol consumption (OR = 0.5, 95%CI 0.2-1.2). The odds ratio was higher among users of drugs that inhibit dihydrofolate reductase (OR = 1.6, 95%CI 0.9-2.8) than drugs that work through other mechanisms (OR = 1.2, 95%CI 0.7-1.9).

CONCLUSIONS

Our data provide little support for the hypothesis that regular folic acid antagonist use increases the risk of colorectal cancer. However, there is a suggestion that dihydrofolate reductase inhibitors specifically may increase the risk.