|Nutrition Evidence Library|
What impact has mandatory folic acid fortification had on the incidence of colon cancer?
A limited body of evidence demonstrates that mandatory folic acid fortification has increased the incidence of colorectal cancer (CRC) in the US and Canada.
Overall strength of the available supporting evidence: Strong; Moderate; Limited; Expert Opinion Only; Grade not assignable For additional information regarding how to interpret grades, click here.
Evidence Summary Overview
Mason et al, 2007 used the nationwide Surveillance, Epidemiology and End Result Registry, which collected data in the US and Canada from 1986 to 2002, to address the question. In the US the absolute rates of colorectal cancer (CRC) began to increase in 1996 and peaked in 1998. In Canada the absolute rates of CRC began to increase in 1997 and peaked in 2000. The sudden increase in CRC incidence represents a significant deviation from the time period just prior to folate fortification in the US by four to six additional cases per 100,000 individuals. It does not appear that changes in colorectal endoscopic procedures accounted for the increase in CRC incidence.
The study of Hirsch et al (2009) compared rates of hospital discharges due to CRC in Chile before (1992 to 1996) and after (2001 to 2004) mandatory folic acid fortification (220mcg per 100g wheat flour). The results were described in two groups: 1) Adults aged 45 to 64 and 2) adults aged 65 to 70. In age group 1, the rate ratio of hospital discharges due to CRC was 2.6 (CI: 99% 2.93 to 2.58) for an overall increase of 162%. In age group 2, the rate ratio was 2.9 (CI: 99% 3.25 to 2.86). The authors conclude that mandatory folate fortification may be associated with an increased risk of colon cancer.
Evidence Summary Paragraphs
Hirsch et al, 2009 (neutral quality). This trend study compared the rates of hospital discharges owing to colon cancer in Chile before (1992 to 1996) and after (2001 to 2004) mandatory fortification with 220mcg folic acid per 100g wheat flour. Results were described for two groups: 1) 45 to 64 years and 2) 65 to 79 years old. In Group 1, the rate of hospital discharges owing to colon cancer increased by 162%. The highest rate ratio between the two periods was for colon cancer in Group 1 (rate ratio, 2.6,CI: 99% 2.93, 2.58) and in Group 2 (rate ratio, 2.9,CI: 99% 3.25, 2.86). These data provide new evidence that a folate fortification program could be associated with risk of colon cancer.
Mason et al, 2007 (neutral quality). This research hypothesis highlights a temporal association between folic acid fortification of enriched cereal grains in the US and Canada and an increase in the incidence of colorectal cancer (CRC) in these two countries. This paper presents a hypothetical foundation on which further research will be required to determine whether causality exists. In the US the absolute rates of CRC began to increase in 1996 and peaked in 1998. In Canada the absolute rates of CRC began to increase in 1997 and peaked in 2000. The sudden increase in CRC incidence represents a statistically significant deviation from the pre-1996 to 1997 trends by four to six additional cases per 100,000 individuals.
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Research Design and Implementation Rating Summary
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Hirsch S, Sanchez H, Albala C, de la Maza MP, Barrera G, Leiva L, Bunout D. Colon cancer in Chile before and after the start of the flour fortification program with folic acid. European Journal of Gastroenterology & Hepatology. 2009; 21: 436-439.
Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, Rosenberg IH. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: A hypothesis. Cancer Epidemiol Biomarkers Prev. 2007 Jul; 16 (7): 1,325-1,329.