title: Heterozygosity for the Cys282Tyr mutation in the HFE gene and the risk of colorectal cancer (Netherlands).
abstract: OBJECTIVE
  Heterozygosity for the Cys282Tyr transition in the HFE-gene is associated with slightly increased iron levels and may therefore be a potential risk factor for colorectal cancer.
  
  
  METHODS
  We studied the relationship between Cys282Tyr-heterozygosity and colorectal cancer using a case-control design. The 240 colorectal cancer cases and 635 controls in our study were derived from a prospective cohort study of 12,242 postmenopausal women, who were invited for an experimental breast cancer screening program in Utrecht, The Netherlands. The women were age 51-69 at time of inclusion and were followed for a period of 20 years. HFE genotyping was performed by PCR and allele-specific oligonucleotide (ASO) hybridization.
  
  
  RESULTS
  The risk of colorectal cancer was higher for women who were heterozygous for the Cys282Tyr mutation, than for those who were Cys282Tyr-wildtypes, although this was not statistically significant (Age-adjusted OR = 1.2, 95% CI: 0.6-2.2). Cys282Tyr-heterozygotes who smoked seemed to be at higher risk of colorectal cancer, although the p-value for interaction was not significant (p-value 0.42).
  
  
  CONCLUSIONS
  The Cys282Tyr mutation is not associated with an increased risk for colorectal cancer in postmenopausal women, although in combination with smoking a slightly increased risk cannot be excluded.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. d.l.vandera@jc.azu.nl
authors.forename: Daphne L
authors.initials: DL
authors.lastname: van der A
authors.forename: Olga
authors.initials: O
authors.lastname: van der Hel
authors.forename: Mark
authors.initials: M
authors.lastname: Roest
authors.forename: Yvonne T
authors.initials: YT
authors.lastname: van der Schouw
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
authors.forename: Joannes J M
authors.initials: JJ
authors.lastname: Marx
authors.forename: Paulus A H
authors.initials: PA
authors.lastname: van Noord
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D003545:Cysteine / Q000235:genetics; D005260:Female; D005838:Genotype; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014443:Tyrosine / Q000235:genetics
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014443:Tyrosine; D003545:Cysteine