The present analysis showed no association between dietary intake of iron, heme iron, iron from meat sources, or non-heme iron and risk of cancer of the colon, rectum, or proximal or distal colon. Red meat intake was associated with increased risk of cancer of the rectum, with evidence of a dose–response relationship. Previous studies are suggestive of an association of red meat intake with colorectal cancer, but the evidence is weak and inconsistent (Potter, 1999
). While potentially reflecting a real association, it is also possible that the result for rectal cancer is a chance finding due to the large number of comparisons. We found no association of any of iron- or meat-related variables with colorectal cancer in women who consumed any amount of alcohol or who consumed 20+
, or in users of HRT.
Three previous studies that have assessed the association between heme iron intake and colon or colorectal cancer have yielded mixed results. In the Iowa Women's Health Cohort, Lee et al (2004)
reported a positive association of heme iron with proximal, but not distal, colon cancer, but only when zinc intake was included in the model. The association was stronger in women who consumed alcohol and strongest in women consuming 10+
of alcohol. Using data from the Swedish Mammography Cohort, Larsson et al (2005)
noted a statistically significant positive association between heme iron intake and colon cancer (principally distal colon cancer) in women who drank 20+
, but not in women drinking <20
. Finally, in an analysis of the Netherlands Cohort Study, Balder et al (2006)
found a positive association between heme iron intake and colon cancer risk in men, but not in women, when cases diagnosed in the first 2 years of follow-up were excluded, but they did not observe an association with rectal cancer. The authors noted an increasing trend in risk of colon cancer in men only with increasing levels of the heme/chlorophyll ratio. They also reported finding a ‘suggestion of an association' of heme iron with colon and rectal cancer in women who drank >5
of alcohol. The studies by Lee et al
and Larsson et al
used a fixed proportion of heme iron (40%) from all types of meat, whereas Balder et al
used differing proportions for different types of meat. We found no association using either method for calculation of heme iron.
Several other studies have examined intake of iron, either from the diet alone or from both diet and supplements, and markers of body iron stores in relation to colorectal cancer risk. In a Finnish cohort study, Knekt et al (1994)
reported that participants with transferrin saturation levels of greater than 60% had a relative risk for colorectal cancer of 3.04 (95% CI: 1.64–5.62). In an analysis of data from the National Health and Nutrition Examination Survey I and the National Health Evaluation Follow-up Study (Wurzelmann et al, 1996
), participants in the highest quartile of dietary iron intake were at increased risk for colon, but not rectal, cancer: relative risk for males and females combined 3.35 (95% CI: 1.74–6.46). In the same study, elevated serum iron was associated with increased risk of distal colon cancer in women only (relative risk, 2.74; 95% CI: 0.82–9.20) and rectal cancer (relative risk, 7.31; 95% CI: 1.13–47.2), whereas transferrin saturation levels and total iron binding capacity (TIBC) were not associated with colorectal cancer. In a nested case–control study carried out within a cohort of New York women (Kato et al, 1999
), no overall associations were seen for levels of serum iron, ferritin, TIBC, transferrin saturation, or for iron intake (diet+supplements) with colorectal cancer. However, there was a significant trend over increasing quartiles of iron intake for cancer of the proximal colon (odds ratio for extreme quartiles 3.29; 95% CI: 0.7–14.6; P
Our study has a number of strengths. The large sample size made it possible to examine subsites within the colorectum. Follow-up of the population is virtually complete. We used two different approaches to estimating heme iron intake, with similar results, and we considered a variety of potential confounding variables as well as possible effect modification due to alcohol consumption and hormone replacement use. However, a number of limitations should also be pointed out. No information was available for iron derived from nutritional supplements, which, in a cohort study from New York (Kato et al, 1999
), accounted for 38% of total iron intake. Additionally, zinc intake, which in two studies (Lee et al, 2004
; Larsson et al, 2005
) was inversely associated with risk of colon cancer, was not estimated from the original dietary database used in this study. Furthermore, only baseline questionnaire information was available, so that it is possible that intake of nutrients, including iron, changed over the long follow-up period, leading to non-differential misclassification of exposure.
In summary, in this large prospective cohort study, we found no suggestion of an association of iron or heme iron intake assessed at baseline with risk of subsequent colorectal cancer or with risk of cancer at subsites within the colorectum. Furthermore, there was no evidence of effect modification by alcohol consumption or hormone replacement use. To determine whether iron intake contributes to the development of colorectal cancer, future studies should improve on the assessment of iron intake by using repeat measurements and obtaining information on use of iron-containing supplements.