Heterozygosity for the Cys282Tyr mutation in the HFE gene and the risk of colorectal cancer (Netherlands)

Cancer Causes Control. 2003 Aug;14(6):541-5. doi: 10.1023/a:1024839528684.


Background & aims: 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.

MeSH terms

  • Aged
  • Case-Control Studies
  • Cohort Studies
  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / genetics*
  • Cysteine / genetics
  • Female
  • Genotype
  • Hemochromatosis Protein
  • Heterozygote*
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Netherlands / epidemiology
  • Odds Ratio
  • Polymerase Chain Reaction / methods
  • Prospective Studies
  • Risk Factors
  • Smoking / adverse effects
  • Tyrosine / genetics


  • HFE protein, human
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Tyrosine
  • Cysteine