The potential for folate to protect against colon cancer remains a question debated in the scientific literature. In part this is fed by short term studies of supplementation and the potential for an adverse effect in this setting where folate may promote the final development of colon cancer. 1 However, across a larger number of studies evidence is confirming that higher folate levels lower long term risk of colon cancer. Let us look at that evidence.
Lee and colleagues recently reviewed the evidence for folate intake and colon cancer development by studying the time course of exposure and risk. 2 This is essential when addressing the potential for prevention . 3 We note that they see a significant reduction in risk of colorectal cancer when they evaluated intake 12 to 16 years before diagnosis. Risk was reduced by 30 percent comparing those who consumed 800 micrograms per day or more against those who consumed less than 250 micrograms per day. Recent intake was not related to risk. To further refine understanding of this association the authors assessed intake in relation to the development of colon polyps, the precursor lesions from which the majority of colon cancers develop. They saw that both long and short term intake of folate were related to significantly lower risk of colon adenomatous polyps. 2
Current use of a multivitamin for 15 or more years reduced risk of colon cancer, but shorter use did not. These results are further supported by the combine data from 13 prospective cohort studies. With over 725,000 participants, these studies included over 5700 cases of colon cancer. 4 Dietary folate was associated with a significant reduction in risk of colon cancer. Further more the risk of colon cancer was reduced in a linear relation with higher intake of folate. A systematic review including 27 studies also showed a significant reduction in risk of colorectal caner. 5 Plasma folate levels also show this protective relation. 6
Across these studies the evidence strongly supports protection against colon cancer. While some studies have not found an effect, this may in large part be attributed to looking too close to the diagnosis of colon cancer – a time when the premalignant lesion ahs already formed. The new evidence on duration emphasizes the importance of long-term exposure to protect against cancer and the need to better focus epidemiologic studies on the appropriate time course of cancer development to improve understanding of the potential for prevention. 7-8
Literature cited
1. Drake BF, Colditz GA. Assessing cancer prevention studies–a matter of time. JAMA : the journal of the American Medical Association. Nov 18 2009;302(19):2152-2153.
2. Lee JE, Willett WC, Fuchs CS, et al. Folate intake and risk of colorectal cancer and adenoma: modification by time. Am J Clin Nutr. Jan 26 2011.
3. Colditz GA, Taylor PR. Prevention trials: their place in how we understand the value of prevention strategies. Annu Rev Public Health. Apr 21 2010;31:105-120.
4. Kim DH, Smith-Warner SA, Spiegelman D, et al. Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer. Cancer Causes Control. Nov 2010;21(11):1919-1930.
5. Kennedy DA, Stern SJ, Moretti M, et al. Folate intake and the risk of colorectal cancer: A systematic review and meta-analysis. Cancer Epidemiol. Feb 2011;35(1):2-10.
6. Wei EK, Giovannucci E, Selhub J, Fuchs CS, Hankinson SE, Ma J. Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women. J Natl Cancer Inst. May 4 2005;97(9):684-692.
7. Colditz GA, Beers C. Active Cancer Prevention. In: Elwood M, Sutcliffe S, eds. Cancer Control. Oxford: Oxford University Press; 2010.
8. Colditz GA. Ensuring long-term sustainability of existing cohorts remains the highest priority to inform cancer prevention and control. Cancer causes & control : CCC. May 2010;21(5):649-656.