© 2005 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Heme Iron, Zinc, Alcohol Consumption, and Risk of Colon Cancer
Affiliations of authors: Department of Preventive Medicine, College of Medicine, Kyungpook National University, Daegu, Korea (DHL); Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN (DRJ,KEA); Department of Nutrition, University of Oslo, Oslo, Norway (DRJ)
Correspondence to: Kristin E. Anderson, PhD, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 2nd St., Suite 300, Minneapolis, MN 55454 (e-mail: anderson_k{at}epi.umn.edu).
Our recent publication (1) linking heme iron positively and dietary zinc inversely with colon cancer among alcohol drinkers was based on biologically driven hypotheses. Our analysis involved the study of interactions, which, in the absence of a biologic basis, are difficult to replicate due to low statistical power. Therefore, we read with interest the letter from Larsson et al. reporting that they closely replicated our findings.
We note, however, that some of their findings are not consistent with ours. In their study, red meat consumption was positively associated with colon cancer, even after adjusting for heme iron, suggesting that heme iron only partly explained the positive association of red meat consumption with colon cancer. In our data, there was no association between red meat consumption and colon cancer after adjusting for heme iron intake. The difference in results between their study and ours may be explained, at least in part, by the possibly imprecise estimates of heme iron intake. In our study, heme iron intake was calculated by assuming that heme iron was 40% of the total iron contained in all meats, as proposed by Monsen (2). Although Larsson et al. did not clearly state how they calculated heme iron, we presume they used a similar strategy. This crude method might be problematic because mean heme iron content in animal foods (e.g., meat, viscera, and blood; fish or other marine animals) varies between 17.4% and 80.8% of the total iron content (3). The consequence of this problem might differ depending on the dietary pattern in a specific population. We note that the correlation coefficient between heme iron and red meat intake was only 0.6 in the Swedish Mammography Cohort compared with almost 0.9 in the Iowa Women's Health Study. To our knowledge, there is no available nutrient database that specifies heme and nonheme iron. The National Cancer Institute is developing a heme-iron database that takes into account cooking methods of meat, which can change the bioavailability of dietary iron (R. Sinha, NCI, personal communication).
The different findings for dietary zinc are also important to note. In our study (1), zinc intake had a clear inverse association with both proximal and distal colon cancers. Larsson et al. also found that dietary zinc had an inverse association, albeit a weak and not statistically significant association. Important food sources of zinc include seafood such as oysters and crabs. If these foods are more commonly consumed in Sweden than in Iowa, then the relatively weak association of zinc intake with colon cancer in the Swedish study might be related to a low validity of zinc intake, which was calculated based on a food frequency questionnaire with 67 food items.
Both studies are important because of the potential etiologic insight they provide. The interaction analyses involve a small proportion of study subjects, and thus the findings might have limited public health significance. Nevertheless, the findings may have general applicability for two reasons. First, in our study, alcohol consumption was chosen as one trigger that can release free iron from the bound form by disturbing iron homeostasis. Theoretically, other triggers such as chronic inflammation might also disturb iron homeostasis. Indeed, in vitro, superoxide or nitric oxide, both of which are produced by stimulated polymorphonuclear leukocytes and macrophages during inflammation, can release iron from ferritin (4,5). Second, oxidative stress is implicated as a common mechanism in the pathogenesis of various diseases (6). We found similar results for diabetes (7) and other chronic diseases (unpublished Iowa Women's Health Study results concerning upper digestive tract cancer, breast cancer, and cardiovascular mortality).
REFERENCES
(1) Lee DH, Anderson KE, Harnack LJ, Folsom AR, Jacobs DR Jr. Heme iron, zinc, alcohol consumption, and colon cancer: Iowa Women's Health Study. J Natl Cancer Inst 2004;96:403–7.
(2) Monsen ER, Balintfy JL. Calculating dietary iron bioavailability: refinement and computerization. J Am Diet Assoc 1982;80:307–11.[Web of Science][Medline]
(3) Boontaveeyuwat N, Klunklin S. The heme iron content of urban and rural Thai diets. J Med Assoc Thai 2001;84:1131–6.[Medline]
(4) Biemond P, van Eijk HG, Swaak AJ, Koster JF. Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes. Possible mechanism in inflammation diseases. J Clin Invest 1984;73:1576–9.[Web of Science][Medline]
(5) Reif DW, Simmons RD. Nitric oxide mediates iron release from ferritin. Arch Biochem Biophys 1990;283:537–41.[CrossRef][Web of Science][Medline]
(6) Droge W. Free radicals in the physiological control of cell function. Physiol Rev 2002;82:47–95.
(7) Lee DH, Folsom AR, Jacobs DR Jr. Dietary iron intake and Type 2 diabetes incidence in postmenopausal women: the Iowa Women's Health Study. Diabetologia 2004;47:185–94.[CrossRef][Web of Science][Medline]
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J Natl Cancer Inst 2005 97: 232-233.
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