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Journal of the National Cancer Institute Advance Access published online on October 12, 2009
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djp346
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© The Author 2009. Published by Oxford University Press.

BRIEF COMMUNICATION

Antagonistic Effects of Aspirin and Folic Acid on Inflammation Markers and Subsequent Risk of Recurrent Colorectal Adenomas

Gloria Y. F. Ho, Xiaonan Xue, Mary Cushman, Gail McKeown-Eyssen, Robert S. Sandler, Dennis J. Ahnen, Elizabeth L. Barry, Fred Saibil, Robert S. Bresalier, Thomas E. Rohan, John A. Baron

Affiliations of authors: Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY (GYFH, XX, TER); Department of Medicine and Department of Pathology, The University of Vermont, Burlington, VT (MC); Department of Public Health Sciences and Department of Nutritional Sciences (GM-E) and Division of Gastroenterology, Department of Medicine (FS), University of Toronto, Toronto, ON, Canada; Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC (RSS); Department of Medicine, Denver Department of Veterans Affairs Medical Center and Department of Medicine, University of Colorado Denver School of Medicine, Denver, CO (DJA); Department of Community and Family Medicine (ELB) and Department of Medicine (JAB), Dartmouth Medical School, Hanover, NH; Department of Gastrointestinal Medicine and Nutrition, MD Anderson Cancer Center, Houston, TX (RSB)

Correspondence to: Gloria Y. F. Ho, PhD, Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461 (e-mail: gloria.ho{at}einstein.yu.edu).

The Aspirin/Folate Polyp Prevention Trial found that aspirin, but not folic acid, reduced recurrence of colorectal adenomas. This study examined whether treatment effects on inflammation markers explained the trial results. The trial had a factorial design with three aspirin (placebo, 81, and 325 mg/d) and two folic acid (placebo and 1 mg/d) groups. There were 884 subjects who had colonoscopic evaluation for adenomas at year 3 and plasma levels of C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor {alpha} (TNF-{alpha}), soluble TNF receptor type II (sTNF-R2), and IL-1 receptor antagonist (IL-1Ra) measured at baseline and year 3. Among individuals not receiving folic acid, there was a 4% decrease (mean ratio of year 3 to baseline levels = 0.96, 95% confidence interval [CI] = 0.82 to 1.14) in CRP for a period of 3 years in the 325 mg of aspirin group vs a 20% increase (mean ratio = 1.20, 95% CI = 1.03 to 1.41) in the placebo group (P = .027). By contrast, the reverse was observed among individuals who also received folic acid (Pinteraction = .013). Changes in inflammation markers were not associated with adenoma recurrence. Low-dose aspirin (325 mg/d) is beneficial in stabilizing CRP levels, which may be abrogated by folate. Nevertheless, inflammation markers do not mediate the chemopreventive effect of aspirin on colorectal adenomas.


CONTEXT AND CAVEATS

Prior knowledge

In the Aspirin/Folate Polyp Prevention Trial, aspirin, but not folic acid, reduced the recurrence of colorectal adenomas.

Study design

Secondary analysis of the Aspirin/Folate Polyp Prevention Trial that examined changes in plasma levels of inflammation markers C-reactive protein (CRP), soluble TNF receptor type II (sTNF-R2), interleukin 6 (IL-6), tumor necrosis factor {alpha} (TNF-{alpha}), and IL-1 receptor antagonist (IL-1Ra) at baseline and at year 3 of 884 subjects. The trial had three aspirin groups (placebo at 81 and 325 mg/d) and two folic acid groups (placebo and 1 mg/d).

Contributions

For subjects who did not receive folic acid, CRP levels in those in the 325 mg/d aspirin group changed very little, whereas it was statistically significantly increased (by 20%) in the placebo group. For subjects who received folic acid, the reverse association was observed. Changes in levels of inflammation markers were not associated with adenoma recurrence.

Implications

Low-dose aspirin may reduce CRP levels, and aspirin in combination with folate may have an opposite effect; however, the markers of inflammation tested in this analysis are likely not involved in the chemopreventive effect of aspirin on colorectal adenomas that was previously observed.

Limitations

Plasma levels rather than tissue levels of the inflammation markers were measured.

From the Editors

 
Manuscript received March 31, 2009; revised August 24, 2009; accepted September 2, 2009.


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