Article
No evidence of increased risk of colorectal cancer in individuals heterozygous for the Cys282Tyr haemochromatosis mutation.
Department of Medicine, The University of Queensland, Queensland Institute of Medical Research, Brisbane, Australia.
Journal of Gastroenterology and Hepatology (impact factor:
2.87).
01/2000;
14(12):1188-91.
pp.1188-91
Source: PubMed
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Citations (0)
- Cited In (3)
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Article: HFE C282Y mutation as a genetic modifier influencing disease susceptibility for chronic myeloproliferative disease.
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ABSTRACT: Iron metabolism has been implicated in carcinogenesis and several studies assessed the potential role of genetic variants of proteins involved in iron metabolism (HFE C282Y, TFR S142G) in different malignancies. Few reports addressed this issue with relation to chronic myeloproliferative disorders (CMPD). The aims of our study were (a) to examine the potential associations of CMPD development with genetic modifiers of iron metabolism in a large cohort of CMPD patients; (b) to examine associations of genetic variants of proteins involved in iron metabolism; and acquired JAK2 V617F mutation with clinical characteristics of CMPD. HFE C282Y was genotyped in 328 CMPD patients and 996 blood donors as controls, HFE H63D, and TFR S142G were tested in CMPD patients and 171 first time blood donors. JAK2 V617F mutation was tested in CMPD patients and in 122 repeated blood donors. Decreased C282Y allele frequency (allele frequency+/-95% confidence interval) was found in the CMPD group (1.8%+/-1.0%) compared with controls (3.4%+/-0.8%; P=0.048). TFR S142G allele frequency was reduced among V617F-negative CMPD patients (34.8%+/-7.6%) compared with controls (47.8%+/-5.4%; P=0.02). The frequency of JAK2 V617F was 75.9% (249 of 328) in the CMPD group. At presentation, elevated hemoglobin levels were found in V617F-positive patients compared with V617F-negative counterparts (P<0.000). Vascular complications (26.6% versus 15.2%; P=0.039) as well as female gender (57.4% versus 41.8%; P=0.019) were more common in V617F-positive patients. We found that HFE C282Y might be associated with a protective role against CMPD. Because chronic iron deficiency or latent anemia may trigger disease susceptibility for CMPD, HFE C282Y positivity may be a genetic factor influencing this effect.Cancer Epidemiology Biomarkers & Prevention 03/2009; 18(3):929-34. · 4.12 Impact Factor -
Article: Blood donation and colorectal cancer incidence and mortality in men.
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ABSTRACT: Although blood donations may reduce body iron stores, to date, prospective data on frequent blood donation and colorectal cancer risk are limited. We tested whether frequent blood donation is associated with a lower risk of colorectal cancer in the Health Professionals Follow-up Study. We prospectively followed 35,121 men who provide the information on lifetime number of blood donations in 1992 through 2008. Serum ferritin levels were measured in a random sample of 305 men. Cox proportional hazard regression models were used to calculate the multivariable relative risks (RRs, 95%CIs) after adjusting for age and other established colorectal cancer risk factors. We documented 684 incident colorectal cancer cases and 224 deaths from colorectal cancer. The mean serum ferritin levels varied from 178 µg/L for men who did not donate blood to 98 µg/L for men who had at least 30 donations. Age-adjusted results for both incidence and mortality were essentially the same as the multivariable-adjusted results. Comparing with non-donors, the multivariable RRs (95%CIs) for colorectal cancer incidence were 0.92 (0.77, 1.11) for 1-5 donation, 0.85 (0.64, 1.11) for 6-9 donations, 0.96 (0.73, 1.26) for 10-19 donations, 0.91 (0.63, 1.32) for 20-29 donations, and 0.97 (0.68, 1.38) for at least 30 donations (P(trend) = 0.92). The multivariable RRs for colorectal cancer mortality were 0.99 (0.72, 1.36) for 1-5 donation, 0.93 (0.57, 1.51) for 6-9 donations, 0.85 (0.50, 1.42) for 10-19 donations, and 1.14 (0.72, 1.83) for at least 20 donations (P(trend) = 0.82). The results did not vary by cancer sub-sites, intake levels of total iron, heme iron, or family history of colorectal cancer. Frequent blood donations were not associated with colorectal cancer incidence and mortality in men. Our results do not support an important role of body iron stores in colorectal carcinogenesis.PLoS ONE 01/2012; 7(6):e39319. · 4.09 Impact Factor -
Article: Heterozygosity for the Cys282Tyr mutation in the HFE gene and the risk of colorectal cancer (Netherlands).
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ABSTRACT: 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. 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. 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). 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.Cancer Causes and Control 08/2003; 14(6):541-5. · 2.88 Impact Factor
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Keywords
23 control subjects
83 females
colorectal cancer
colorectal carcinoma
Cys282Tyr mutation
digestion
haemochromatosis gene
Heterozygosity
HFE
increased body iron stores
increased risk
patients
Previous studies
relative risk 0.90
risk factor
Rsa1
sporadic colorectal carcinoma
tumour site
unselected patients
