Heterozygosity for the Cys282Tyr mutation in the HFE gene and the risk of colorectal cancer (Netherlands).
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.
van der A
Daphne L
DL
Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. d.l.vandera@jc.azu.nl
van der Hel
Olga
O
Roest
Mark
M
van der Schouw
Yvonne T
YT
van Gils
Carla H
CH
Marx
Joannes J M
JJ
van Noord
Paulus A H
PA
Peeters
Petra H M
PH
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
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014443:Tyrosine; D003545:Cysteine