Journal of the National Cancer Institute Advance Access originally published online on March 10, 2009
JNCI Journal of the National Cancer Institute 2009 101(6):432-435; doi:10.1093/jnci/djp019
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author 2009. Published by Oxford University Press.
BRIEF COMMUNICATION |
Folic Acid and Risk of Prostate Cancer: Results From a Randomized Clinical Trial
Affiliations of authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (JCF, RWH); Departments of Medicine and Community and Family Medicine, Dartmouth Medical School, Hanover, NH (MVG, JAB); Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC (RSS); Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA (RWS); Department of Gastrointestinal Medicine and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX (RSB); Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH (CAB); Dalla Lana School of Public Health and Department of Nutritional Sciences, University of Toronto, Toronto, Canada (GEM-E)
Correspondence to: Jane C. Figueiredo, PhD, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (e-mail: janefigu{at}usc.edu).
Data regarding the association between folate status and risk of prostate cancer are sparse and conflicting. We studied prostate cancer occurrence in the Aspirin/Folate Polyp Prevention Study, a placebo-controlled randomized trial of aspirin and folic acid supplementation for the chemoprevention of colorectal adenomas conducted between July 6, 1994, and December 31, 2006. Participants were followed for up to 10.8 (median = 7.0, interquartile range = 6.0–7.8) years and asked periodically to report all illnesses and hospitalizations. Aspirin alone had no statistically significant effect on prostate cancer incidence, but there were marked differences according to folic acid treatment. Among the 643 men who were randomly assigned to placebo or supplementation with folic acid, the estimated probability of being diagnosed with prostate cancer over a 10-year period was 9.7% (95% confidence interval [CI] = 6.5% to 14.5%) in the folic acid group and 3.3% (95% CI = 1.7% to 6.4%) in the placebo group (age-adjusted hazard ratio = 2.63, 95% CI = 1.23 to 5.65, Wald test P = .01). In contrast, baseline dietary folate intake and plasma folate in nonmultivitamin users were inversely associated with risk of prostate cancer, although these associations did not attain statistical significance in adjusted analyses. These findings highlight the potential complex role of folate in prostate cancer and the possibly different effects of folic acid–containing supplements vs natural sources of folate.
| CONTEXT AND CAVEATS Prior knowledge Some observational studies had suggested that increased folate in the diet might lower the risk of prostate cancer. Study design This study addressed the effect of folic acid supplementation on risk of prostate cancer in the context of a double-blind randomized clinical trial of folic acid and/or aspirin for prevention of colorectal adenoma. Dietary intake of folate was assessed at baseline. Contribution Folic acid supplementation was associated with increased risk of prostate cancer. By contrast, baseline dietary folate was inversely associated with prostate cancer risk. Implications Folate metabolism may have a complex role in prostate cancer; the effects of folic acid–containing supplements on the risk of prostate cancer may be different those of natural dietary sources. Limitations Given the small number of prostate cancers in this study, the estimates of prostate cancer risk in the placebo and folic acid groups should be interpreted with caution. From the Editors
|
Manuscript received July 2, 2008; revised December 11, 2008; accepted January 16, 2009.
Related Article in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2009 101: 361.
This article has been cited by other articles:
|
|
 |
|
  U. C Ericson, M. I. Ivarsson, E. Sonestedt, B. Gullberg, J. Carlson, H. Olsson, and E. Wirfalt Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele Am. J. Clinical Nutrition, November 1, 2009; 90(5): 1380 - 1389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Bailey and J. E. Ayling From the Cover: The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake PNAS, September 8, 2009; 106(36): 15424 - 15429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Collin, C. Metcalfe, L. Zuccolo, S. J. Lewis, L. Chen, A. Cox, M. Davis, J. A. Lane, J. Donovan, G. D. Smith, et al. Association of Folate-Pathway Gene Polymorphisms with the Risk of Prostate Cancer: a Population-Based Nested Case-Control Study, Systematic Review, and Meta-analysis Cancer Epidemiol. Biomarkers Prev., September 1, 2009; 18(9): 2528 - 2539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Lindzon, A. Medline, K.-J. Sohn, F. Depeint, R. Croxford, and Y.-I. Kim Effect of folic acid supplementation on the progression of colorectal aberrant crypt foci Carcinogenesis, September 1, 2009; 30(9): 1536 - 1543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Excess Risk for Prostate Cancer with Folic Acid Supplementation Journal Watch (General), March 26, 2009; 2009(326): 2 - 2. [Full Text]
|
|