Iron intake, body iron stores and colorectal cancer risk in women: a nested case-control study.

Nelson Institute of Environmental Medicine and Kaplan Comprehensive Cancer Center, New York University School of Medicine, NY 10016, USA.
International Journal of Cancer (Impact Factor: 5.09). 04/1999; 80(5):693-8.
Source: PubMed


Accumulated evidence suggests that increased body iron stores may increase the risk of colorectal cancer, possibly via catalyzing oxidation reactions. We examined the relationship between iron status and colorectal cancer in a case-control study nested within the New York University Women's Health Study cohort. For 105 incident cases of colorectal cancer with an average follow-up of 4.7 years and 523 individually matched controls, baseline levels of serum iron, ferritin, total iron binding capacity (TIBC) and transferrin saturation were determined as indicators of body iron stores, and total iron intake was assessed based on their diet and supplement intake. Overall, there were no associations between the risk of colorectal cancer and any of these indices except for serum ferritin, which showed a significant inverse association. When analyzed by subsite, there was an increasing trend in risk of cancer of the proximal colon with increasing total iron intake (p-value for trend = 0.04). In addition, a significantly increased risk of colorectal cancer associated with higher total iron intake [odds ratio (OR) = 2.50; 95% confidence interval (CI): 1.06-5.87] was observed among subjects with higher intake of total fat. Our results do not support a role of increased body iron stores in the development of colorectal cancer, but suggest that luminal exposure to excessive iron may possibly increase the risk in combination with a high fat diet.

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    • "In addition, excess iron can mediate reactive oxygen species through Fenton reaction chemistry, resulting in lipid, protein, and DNA damage (Toyokuni, 1996). A link between excess iron and cancer incidence in CRC has been reported (Chua et al., 2010; Kato et al., 1999; Lee et al., 2004; Mainous et al., 2005; Nelson, 2001; Toyokuni, 2009; Weinberg, 1994, 1996). Most notably, a meta-analysis of 33 epidemiological studies showed that 75% of studies supported an association between excess iron and CRC risk (Nelson, 2001). "
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    ABSTRACT: It is clear from epidemiological studies that excess iron is associated with increased risk of colorectal cancer; however, questions regarding the mechanism of how iron increases cancer risk, the source of the excess iron (circulating or luminal), and whether iron reduction represents a potential therapeutic option remain unanswered. In this study, we show that after Apc deletion, the cellular iron acquisition proteins TfR1 and DMT1 are rapidly induced. Conversely, restoration of APC reduces cellular iron due to repression of these proteins. To test the functional importance of these findings, we performed in vivo investigations of the impact of iron levels on intestinal tumorigenesis. Strikingly, depletion of luminal (but not systemic) iron strongly suppressed murine intestinal tumorigenesis, whereas increased luminal iron strongly promoted tumorigenesis. Taken together, our data definitively delineate iron as a potent modifier of intestinal tumorigenesis and have important implications for dietary iron supplementation in patients at high risk of colorectal cancer.
    Cell Reports 08/2012; 2(2):270-82. DOI:10.1016/j.celrep.2012.07.003 · 8.36 Impact Factor
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    • "Meat is a source of several multisite carcinogens including N-nitroso compounds, heterocyclic amines, and polycyclic aromatic hydrocarbons, some of which are formed during high-temperature cooking of meat [2]. Iron in red meat may increase oxidative damage and increase the formation of N-nitroso compounds [6]. Meat is also a major source of saturated fat which has been positively associated with cancer [7]. "
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    ABSTRACT: There is emerging evidence for a beneficial effect of meat consumption on the musculoskeletal system. However, whether it affects the risk of knee and hip osteoarthritis is unknown. We performed a prospective cohort study to examine the relationship between meat consumption and risk of primary hip and knee replacement for osteoarthritis. Eligible 35,331 participants were selected from the Melbourne Collaborative Cohort Study recruited during 1990-1994. Consumption of fresh red meat, processed meat, chicken, and fish was assessed using a food frequency questionnaire. Primary hip and knee replacement for osteoarthritis during 2001-2005 was determined by linking the cohort records to the Australian National Joint Replacement Registry. There was a negative dose-response relationship between fresh red meat consumption and the risk of hip replacement (hazard ratio (HR) 0.94 per increase in intake of one time/week, 95% confidence interval (CI) 0.89-0.98). In contrast, there was no association with knee replacement risk (HR 0.98, 95% CI 0.94-1.02). Consumption of processed meat, chicken and fish were not associated with risk of hip or knee replacement. A high level consumption of fresh red meat was associated with a decreased risk of hip, but not knee, joint replacement for osteoarthritis. One possible mechanism to explain these differential associations may be via an effect of meat intake on bone strength and hip shape. Further confirmatory studies are warranted.
    BMC Musculoskeletal Disorders 01/2011; 12:17. DOI:10.1186/1471-2474-12-17 · 1.72 Impact Factor
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    • "Free iron is a pro-oxidant, and may contribute to colorectal carcinogenesis by promoting free radical production and lipid peroxidation (Nelson, 1992; Toyokuni, 1996; Huang, 2003). Epidemiologic studies examining the association of iron intake and markers of body iron stores with risk of colorectal cancer or colorectal polyps have yielded some evidence of positive associations (Knekt et al, 1994; Bird et al, 1996; Wurzelmann et al, 1996; Tseng et al, 1997; Kato et al, 1999). In addition, epidemiologic studies have shown a modest association between red meat intake, the major source of dietary iron, and risk of colon and colorectal cancer (Norat and Riboli, 2001; Larsson and Wolk, 2006). "
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    ABSTRACT: In a cohort study of 49,654 Canadian women, we assessed the association of colorectal cancer with total iron and heme iron intake, excluding iron supplements. Among women aged 40-59 years, followed for an average of 16.4 years, we identified 617 incident colorectal cancer cases. Data from a food frequency questionnaire administered at baseline were used to calculate red meat intake and intake of total dietary iron, iron from meat, and heme iron. Analyses were carried out for all cases and for the proximal colon, distal colon, and rectum, using Cox proportional hazards models. We found no association of intake of iron, heme iron, or iron from meat with risk of colorectal cancer overall or with any of the subsites, nor was there effect modification by alcohol consumption or hormonal replacement therapy.
    British Journal of Cancer 08/2007; 97(1):118-22. DOI:10.1038/sj.bjc.6603837 · 4.84 Impact Factor
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