Affiliations of authors: Division of Nutritional Epidemiology, The National Institute of Environmental Medicine (SCL, AW), and Department of Medical Epidemiology and Biostatistics (HOA), Karolinska Institutet, Stockholm, Sweden; Departments of Epidemiology and Nutrition, Harvard School of Public Health, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA (EG)
Correspondence to: Susanna C. Larsson, Division of Nutritional Epidemiology, The National Institute of Environmental Medicine, Karolinska Institutet, P.O. Box 210, SE-171 77 Stockholm, Sweden (e-mail: susanna.larsson{at}imm.ki.se).
Lee et al. (1) recently reported a positive association of heme iron intake and an inverse association of zinc intake with the risk of colon cancer among women who consumed alcohol. To examine these associations further, we analyzed data from the population-based Swedish Mammography Cohort of 61 433 women who were aged 4075 years and without cancer at baseline in 19871990 (2). Intake of heme iron and zinc was assessed at baseline and in 1997 using self-administered food frequency questionnaires. The data met the proportional hazards assumptions, and we computed rate ratios (RRs) using Cox proportional hazards models stratified on age in months and calendar time. To reduce within-person variation and to best represent long-term diet (3), we used the baseline and the 1997 dietary intake measurements; in these analyses, the dietary data from the baseline questionnaire were used for follow-up from 1987 through 1997 and the average of dietary intakes from baseline and 1997 was used for the period from 1998 through June 2004. The Ethics Committees at the Karolinska Institutet (Stockholm) and the Uppsala University Hospital approved this study.
During a mean of 14.8 years of follow-up, from March 1987 through June 2004, 547 women were diagnosed as having colon cancer. After controlling for potential confounders, we observed a statistically significant positive association between heme iron intake and colon cancer risk (Table 1) among women who consumed at least 20 g/week of alcohol (multivariable RR comparing top and bottom quintiles of heme iron intake = 2.29, 95% confidence interval [CI] = 1.25 to 4.21). The comparable RR among women who consumed less than 20 g/week of alcohol was 1.05 (95% CI = 0.74 to 1.48). A test for interaction between heme iron and alcohol in relation to colon cancer risk was statistically significant (P = .01). High consumption of red meat, the main source of heme iron, was also associated with an increased risk of colon cancer among women with an alcohol consumption of at least 20 g/week; the multivariable RR adjusted for the same variables as in Table 1 except for heme iron was 2.85 (95% CI = 1.30 to 6.26) for women in the highest quintile compared with those in the lowest quintile of red meat consumption. When we included heme iron and red meat simultaneously in a multivariable model (Spearman correlation coefficient = 0.6), the RR comparing extreme quintiles was 1.78 (95% CI = 0.87 to 3.65) for heme iron intake and 1.93 (95% CI = 0.76 to 4.90) for red meat consumption. There were too few cases among women who consumed at least 20 g/week of alcohol to examine subsites in the colon. We found no statistically significant linear association between zinc intake and colon cancer risk (Table 1).
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In summary, in this large population-based cohort study, both heme iron and red meat intake, when mutually adjusted, showed a positive association with the risk of colon cancer among women who consumed alcohol. These findings suggest that heme iron may only partly explain the apparent increased risk of colon cancer associated with a high red meat consumption and that other factors in red meat may be implicated in colon carcinogenesis.
NOTES
Support was provided by research grants from the Swedish Cancer Foundation, the Swedish Research Council/Longitudinal Studies, and the Swedish Foundation for International Cooperation in Research and Higher Education (STINT).
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;96:4037.
(2) Larsson SC, Rafter J, Holmberg L, Bergkvist L, Wolk A. Red meat consumption and risk of cancers of the proximal colon, distal colon and rectum: The Swedish Mammography Cohort. Int J Cancer 2005;113:82934.[Medline]
(3) Hu FB, Stampfer MJ, Rimm E, Ascherio A, Rosner BA, Spiegelman D, Willett WC. Dietary fat and coronary heart disease: a comparison of approaches for adjusting for total energy intake and modeling repeated dietary measurements. Am J Epidemiol 1999;149:53140.[Abstract]
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