Showing papers by "Dale C. Snover published in 2007"

Folic acid for the prevention of colorectal adenomas: a randomized clinical trial.

Abstract: ContextLaboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine.ObjectiveTo assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas.Design, Setting, and ParticipantsA double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma.InterventionParticipants were randomly assigned in a 1:1 ratio to receive 1 mg/d of folic acid (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles (the first interval was at 3 years and the second at 3 or 5 years later).Main Outcome MeasuresThe primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions (≥25% villous features, high-grade dysplasia, size ≥1 cm, or invasive cancer) and adenoma multiplicity (0, 1-2, or ≥3 adenomas).Results During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [CI], 0.90-1.20; P = .58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n = 57) and 8.6% for placebo (n = 42) (unadjusted RR, 1.32; 95% CI, 0.90-1.92; P = .15). A total of 607 participants (59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n = 113) (unadjusted RR, 1.13; 95% CI, 0.93-1.37; P = .23); and incidence of at least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation. ConclusionsFolic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.Trial Registration clinicaltrials.gov Identifier: NCT00272324

Folic acid for the prevention of colorectal adenomas: A randomized clinical trial. Editorial

Abstract: Context Laboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine. Objective To assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas. Design, Setting, and Participants A double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6,1994, and October 1,2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma. Intervention Participants were randomly assigned in a 1:1 ratio to receive 1 mg/d of folic acid (n = 516) or placebo (n=505), and were separately randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles (the first interval was at 3 years and the second at 3 or 5 years later). Main Outcome Measures The primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions ( ≥25% villous features, high-grade dysplasia, size ≥1 cm, or invasive cancer) and adenoma multiplicity (0,1-2, or ≥3 adenomas). Results During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1 % for folic acid (n =221) and 42.4% for placebo (n =206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [Cl], 0.90-1.20; P=.58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n =57) and 8.6% for placebo (n =42) (unadjusted RR, 1.32; 95% Cl, 0.90-1.92; P=.15). A total of 607 participants (59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n=113) (unadjusted RR, 1.13; 95% Cl, 0.93-1.37; P=.23); and incidence of at least 1 advanced lesion was 11.6% for folic acid (n =35) and 6.9% for placebo (n=21) (unadjusted RR, 1.67; 95% Cl,1.00-2.80; P=.05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation. Conclusions Folic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.

Prolonged Effect of Calcium Supplementation on Risk of Colorectal Adenomas in a Randomized Trial

Abstract: Background Calcium supplementation has been shown to decrease the risk of recurrence of colorectal adenomas in randomized trials. However, the duration of this protective effect after cessation of active supplementation is not known. Methods In the Calcium Polyp Prevention Study, 930 subjects with a previous colorectal adenoma were randomly assigned from November 1988 through April 1992 to receive placebo or 1200 mg of elemental calcium daily for 4 years. The Calcium Follow-up Study was an observational phase of the trial that tracked adenoma occurrence for an average of 7 years after the end of randomized treatment and gathered information regarding the use of medications, vitamins, and supplements during that time. We obtained follow-up information for 822 subjects, 597 of whom underwent at least one colonoscopy after the end of study treatment and are included in this analysis. Generalized linear models were used to compute relative risks (RRs) and 95% confidence intervals (CIs) for the effect of randomized calcium treatment on risk of adenoma recurrence during the first 5 years after study treatment ended and during the subsequent 5 years. Statistical tests were two-sided. Results During the first 5 years after randomized treatment ended, subjects in the calcium group still had a substantially and statistically significantly lower risk of any adenoma than those in the placebo group (31.5% versus 43.2%; adjusted RR = 0.63, 95% CI = 0.46 to 0.87, P = .005) and a smaller and not statistically significant reduction in risk of advanced adenomas (adjusted RR = 0.85, 95% CI = 0.43 to 1.69, P = .65). However, the randomized treatment was not associated with the risk of any type of polyp during the next 5 years. The findings were broadly similar when the analysis was restricted to subjects who did not report use of any calcium supplements after the treatment phase of the trial ended. Conclusion The protective effect of calcium supplementation on risk of colorectal adenoma recurrence extends up to 5 years after cessation of active treatment, even in the absence of continued supplementation.