TY - JOUR
T1 - Folic acid supplementation and risk of colorectal neoplasia during long-term follow-up of a randomized clinical trial
AU - Passarelli, Michael N.
AU - Barry, Elizabeth L.
AU - Rees, Judy R.
AU - Mott, Leila A.
AU - Zhang, Dongyu
AU - Ahnen, Dennis J.
AU - Bresalier, Robert S.
AU - Haile, Robert W.
AU - McKeown-Eyssen, Gail
AU - Snover, Dale C.
AU - Cole, Bernard F.
AU - Baron, John A.
N1 - Publisher Copyright:
© 2019 American Society for Nutrition.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Background: The Aspirin/Folate Polyp Prevention Study previously found folic acid increased risk of advanced and multiple colorectal adenomas during a surveillance colonoscopy interval starting about 3 y after randomization. Objective: We conducted secondary analyses to evaluate folic acid effects with additional follow-up after treatment was stopped. Methods: In total, 1021 participants recently diagnosed with colorectal adenomas were randomly assigned to 1 mg/d of folic acid (n = 516) or placebo (n = 505), with or without aspirin, beginning 6 July 1994. The original 3-y treatment period was extended into a subsequent colonoscopy interval, but eventually stopped prematurely on 1 October 2004. With additional post-treatment follow-up, a total of 663 participants who extended treatment completed a second colonoscopic surveillance interval after the initial 3-y follow-up. In addition, 490 participants provided information regarding a subsequent surveillance colonoscopy occurring before completion of follow-up on 31 May 2012, including 325 who had agreed to extended treatment. Study endpoints included conventional adenomas, sessile serrated adenomas/polyps (SSA/Ps), or colorectal cancer, and RRs with 95% CIs were adjusted for baseline characteristics associated with availability of follow-up. Results: Among those who extended treatment, any colorectal neoplasia was found in 118 (36%) participants assigned to placebo and 146 (43%) assigned to folic acid during the second surveillance interval (RR: 1.21; 95% CI: 0.99, 1.47; P = 0.06). Increased risk of SSA/P with extended folic acid supplementation was statistically significant during the second surveillance interval (RR: 1.94; 95% CI: 1.02, 3.68; P = 0.04). There was no evidence of post-treatment effects for any colorectal neoplasia (RR: 1.01; 95% CI: 0.80, 1.28; P = 0.94), and the post-treatment effect for SSA/P was no longer statistically significant (RR: 1.38; 95% CI: 0.59, 3.19; P = 0.46). Conclusions: Delayed treatment effects were not observed, but folic acid may increase SSA/P risk. This trial was registered at clinicaltrials.gov as NCT00272324.
AB - Background: The Aspirin/Folate Polyp Prevention Study previously found folic acid increased risk of advanced and multiple colorectal adenomas during a surveillance colonoscopy interval starting about 3 y after randomization. Objective: We conducted secondary analyses to evaluate folic acid effects with additional follow-up after treatment was stopped. Methods: In total, 1021 participants recently diagnosed with colorectal adenomas were randomly assigned to 1 mg/d of folic acid (n = 516) or placebo (n = 505), with or without aspirin, beginning 6 July 1994. The original 3-y treatment period was extended into a subsequent colonoscopy interval, but eventually stopped prematurely on 1 October 2004. With additional post-treatment follow-up, a total of 663 participants who extended treatment completed a second colonoscopic surveillance interval after the initial 3-y follow-up. In addition, 490 participants provided information regarding a subsequent surveillance colonoscopy occurring before completion of follow-up on 31 May 2012, including 325 who had agreed to extended treatment. Study endpoints included conventional adenomas, sessile serrated adenomas/polyps (SSA/Ps), or colorectal cancer, and RRs with 95% CIs were adjusted for baseline characteristics associated with availability of follow-up. Results: Among those who extended treatment, any colorectal neoplasia was found in 118 (36%) participants assigned to placebo and 146 (43%) assigned to folic acid during the second surveillance interval (RR: 1.21; 95% CI: 0.99, 1.47; P = 0.06). Increased risk of SSA/P with extended folic acid supplementation was statistically significant during the second surveillance interval (RR: 1.94; 95% CI: 1.02, 3.68; P = 0.04). There was no evidence of post-treatment effects for any colorectal neoplasia (RR: 1.01; 95% CI: 0.80, 1.28; P = 0.94), and the post-treatment effect for SSA/P was no longer statistically significant (RR: 1.38; 95% CI: 0.59, 3.19; P = 0.46). Conclusions: Delayed treatment effects were not observed, but folic acid may increase SSA/P risk. This trial was registered at clinicaltrials.gov as NCT00272324.
KW - clinical trial
KW - colorectal adenoma
KW - colorectal cancer
KW - folic acid
KW - sessile serrated adenoma/polyp
UR - http://www.scopus.com/inward/record.url?scp=85072747605&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072747605&partnerID=8YFLogxK
U2 - 10.1093/ajcn/nqz160
DO - 10.1093/ajcn/nqz160
M3 - Article
C2 - 31401653
AN - SCOPUS:85072747605
SN - 0002-9165
VL - 110
SP - 903
EP - 911
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 4
ER -