Plasma Ferrtin, Iron Intake, and the Risk of Colorectal Polyps

Bird, Cristy L.; Witte, John S.; Swendseid, Marian E.; Shikany, James M.; Hunt, Isabelle F.; Frankl, Harold D.; Lee, Eric R.; Longnecker, Matthew P.; Haile, Robert W.

doi:10.1093/oxfordjournals.aje.a008852

Cited by 73 publications

(63 citation statements)

References 35 publications

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“…With greater variability of serum iron, a single measurement would include a large degree of measurement error and, as a consequence, observed association such as relative risk would be increasingly attenuated. Therefore, the low reliability coefficient of serum iron, as shown here, may contribute to the apparent discrepancies of the results observed in previous studies [15][16][17][18]20,21].…”

Section: Discussioncontrasting

confidence: 77%

“…Although other studies reported either no association or an inverse association [17,18], this discrepancy may be due to the fact that the iron measured in these studies represents only a small fraction (<1%) of the total iron in the body [19]. Serum iron, which is the iron stored in transferrin, total iron-binding capacity, which is the total level of transferrin when 100% saturated with iron, and percentage saturation of transferrin were used as biological indices of body iron storage in these studies [15][16][17][18]20,21]. In contrast, ferritin, an iron storage protein, has rarely been measured.…”

Section: Introductionmentioning

confidence: 99%

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Reliability of serum iron, ferritin, nitrite, and association with risk of renal cancer in women

Ali

Akhmedkhanov

Zeleniuch-Jaquotte

et al. 2003

Cancer Detection and Prevention

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Reliability of serum levels of iron, ferritin and nitrite (NO 2 − ) over a 2-year period were evaluated in 40 healthy women (20 pre-menopausal and 20 post-menopausal), ages 39-65 years, from the New York University Women's Health Study (NYUWHS). Three blood samples per woman collected at yearly intervals were analyzed. Reliability coefficients (RCs) of serum iron, ferritin, and nitrite were 0.03 (95% confidence interval ( In a case-control study nested within NYUWHS cohort, serum levels of nitrite, ferritin, and iron were measured in women apparently healthy at the time of blood donation but diagnosed with renal cancer 1.8-12.2 years later (n = 24) and in individually matched controls (two per case). The results suggest that high serum levels of ferritin and nitrite may be associated with a decreased risk of renal cancer (odds ratio (OR), 0.55, 95% CI, 0.15-2.01 for ferritin, and OR, 0.52, 95% CI, 0.17-1.60 for nitrite in women with above median level as compared to women with below median level). The possible role of ferritin and nitrite in renal cancer is discussed.

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Section: Discussioncontrasting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Reliability of serum iron, ferritin, nitrite, and association with risk of renal cancer in women

Ali

Akhmedkhanov

Zeleniuch-Jaquotte

et al. 2003

Cancer Detection and Prevention

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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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confidence: 99%

A cohort study of dietary iron and heme iron intake and risk of colorectal cancer in women

et al. 2007

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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. 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). However, few studies have examined the association of intake of heme iron, derived principally from red meat, with colorectal cancer risk. Heme iron, which has greater bioavailability compared to non-heme iron, has been shown experimentally to have cytotoxic and hyperproliferative effects in the rat colon (Sesink et al, 1999). To date, three cohort studies have reported on the association of heme iron intake and risk of colon or colorectal cancer (Lee et al, 2004;Larsson et al, 2005;Balder et al, 2006), and suggest a possible positive association of intake with risk, which may be enhanced in consumers of alcohol. However, there are inconsistencies in the association found in these studies by subsite (Lee et al, 2004;Larsson et al, 2005) and by sex (Balder et al, 2006), as well as with regard to the role of effect modification by alcohol consumption. We used data from a large cohort study of Canadian women to assess the risk of colorectal cancer in association with total iron and heme iron intake, as well as potential effect modification by alcohol consumption and hormone replacement use. METHODS AND MATERIALS Study populationOur investigation was conducted in the Canadian National Breast Screening Study (NBSS), a randomised controlled trial of screening for breast cancer, which has been described in detail elsewhere (Miller et al, 1992;Terry et al, 2002). In brief, 89 835 women aged 40 -59 years were recruited from the general Canadian population between 1980 and 1985. On enrolment into the study, information was obtained from participant...

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“…Our findings replicate an association with colon cancer but not rectal cancer in one earlier study, 37 whereas others have reported effects of iron on cancers of the rectum and distal colon. 33,39,40 It has been suggested that colon and rectal cancers have different etiologies, 41 although it is not clear why iron would only exert effects in specific sub-sites.…”

Section: Discussionmentioning

confidence: 99%

Iron and colorectal cancer risk in the α‐tocopherol, β‐carotene cancer prevention study

Cross

Gunter

Wood

et al. 2006

Intl Journal of Cancer

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In vitro and in vivo studies have associated iron with both the initiation and promotional stages of carcinogenesis. We investigated whether iron was associated with colorectal cancer in a nested case-control study within the a-tocopherol, b-carotene cancer prevention study cohort. Exposure was assessed at baseline, using a 276-item food frequency questionnaire and a fasting serum sample. The study included 130 colorectal cancer cases (73 colon cancers and 57 rectal cancers) and 260 controls. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Supplemental iron intake was only reported for 4 cases and 18 controls; therefore, we were unable to obtain meaningful results for this variable. Comparing the highest to the lowest quartiles, there was an inverse association between serum ferritin and colorectal cancer risk (OR 5 0.4, 95% CI 5 0.2-0.9) and a suggestion of an inverse association between dietary iron and colorectal cancer risk (OR 5 0.4, 95% CI 5 0.1-1.1). In addition, serum ferritin, serum iron and transferrin saturation were all inversely associated with colon cancer risk specifically (OR 5 0.2, 95% CI 5 0.1-0.7, p trend 5 0.02; OR 5 0.2, 95% CI 5 0.1-0.9, p trend 5 0.05; OR 5 0.1, 95% CI 5 0.02-0.5, p trend 5 0.003, respectively), whereas serum unsaturated iron binding capacity was positively associated with colon cancer risk (OR 5 4.7, 95% CI 5 1.4-15.1, p trend 5 0.009). In summary, we found a significant inverse association between several serum iron indices and colon cancer risk. ' 2006 Wiley-Liss, Inc.Key words: red meat; iron; colorectal cancer There is increasing epidemiological evidence implicating red meat as a risk factor for colorectal cancer, whereas white meat has not been associated with this cancer. 1 One of the main differences between red and white meat is the higher iron content in red meat.There are many mechanisms through which iron might influence the carcinogenic process, particularly with respect to colorectal cancer. Iron is able to catalyze the formation of reactive oxygen species, which can induce oxidative DNA damage. 2 In addition, rodent studies have shown that iron is associated with increased crypt cell proliferation in the large intestine 3 and an increased rate of tumor growth in chemically-induced colorectal cancer. 4,5 Heme iron specifically, which is mainly found in meat, has been associated with increased cytotoxicity of fecal water from rodents, 6 increased endogenous formation of carcinogenic N-nitroso compounds 7 and promotion of chemically-induced colorectal cancer in rats. 8 Of the 3 large cohort studies to address the association between iron and colorectal cancer, one examined dietary iron intake and found a significant positive association between iron consumption and cancer of the proximal colon. 9 All 3 cohorts examined iron stores and colorectal cancer risk; one cohort found increased risks for both colon and rectal tumors 9 and one found an increased risk for rectal cancer in women only, 10 but the th...

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Plasma Ferrtin, Iron Intake, and the Risk of Colorectal Polyps

Cited by 73 publications

References 35 publications

Reliability of serum iron, ferritin, nitrite, and association with risk of renal cancer in women

Reliability of serum iron, ferritin, nitrite, and association with risk of renal cancer in women

A cohort study of dietary iron and heme iron intake and risk of colorectal cancer in women

Iron and colorectal cancer risk in the α‐tocopherol, β‐carotene cancer prevention study

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