title: Hemochromatosis gene mutations, body iron stores, dietary iron, and risk of colorectal adenoma in women.
abstract: BACKGROUND
  Some experimental evidence suggests that iron may play a role in colorectal carcinogenesis, but human data for this role have been conflicting, possibly because of problems related to study design or measurement of iron exposure. We assessed dietary iron intake and genetic and biochemical markers of iron status in a prospective, nested case-control study of women enrolled in the Nurses' Health Study.
  
  
  METHODS
  Among 32 826 women who provided a blood specimen, we identified 527 women with colorectal adenoma and 527 matched control subjects who underwent endoscopy but were not diagnosed with adenoma after blood collection. We assessed iron intake, mutations in the HFE gene that are associated with hereditary hemochromatosis (i.e., H63D and C282Y), and plasma biochemical measures of total body iron, including transferrin saturation and the ratio of the concentrations of transferrin receptors to ferritin. Logistic regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). All statistical tests were two-sided.
  
  
  RESULTS
  Women with any HFE gene mutation had higher total body iron stores, as reflected by higher transferrin saturations (P < .001) and lower levels of the ratio of transferrin receptors to ferritin (P = .02), than women with no HFE gene mutation. However, HFE gene mutations were not associated with risk of adenoma (multivariable RR = 1.08, 95% CI = 0.83 to 1.39; P = .58). Moreover, comparison of extreme categories showed no associations between adenoma and the extent of transferrin saturation (multivariable RR = 0.96, 95% CI = 0.63 to 1.47; Ptrend = .66), the ratio of transferrin receptors to ferritin (multivariable RR = 0.98, 95% CI, 0.60 to 1.60; Ptrend = .99), or dietary iron intake (multivariable RR = 1.04, 95% CI = 0.68 to 1.57; Ptrend = .94).
  
  
  CONCLUSIONS
  Although our study used several distinct measures of iron status (i.e., genetic mutations, biochemical markers, and dietary intake) and a nested case-control design, we did not observe a role for iron in the pathogenesis of colorectal neoplasia in women.
authors.affiliation: Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. achan@partners.org
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tranah
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
mesh_terms: D000236:Adenoma / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000378:metabolism; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019266:Iron, Dietary / Q000008:administration & dosage*; D016015:Logistic Models; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009726:Nurses / Q000706:statistics & numerical data; D016017:Odds Ratio; D011446:Prospective Studies; D011990:Receptors, Transferrin / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014168:Transferrin / Q000378:metabolism; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D019266:Iron, Dietary; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D005293:Ferritins; D007501:Iron