Cancer risk in HFE C282Y homozygotes: results from the HUNT 2 study

Abstract

Objective. In addition to hepatocellular cancer, HFE C282Y homozygotes are reported to have increased risk of colorectal cancer and breast cancer. This study was done to further explore the cancer risk in C282Y homozygotes. Material and methods. We studied cancer incidence in 292 homozygotes and 62,568 others that participated in the HUNT 2 population screening in 1995–1997. Using Cox proportional hazard models, we estimated cancer hazard ratio as a function of C282Y homozygosity and several screening variables including serum transferrin saturation, alcohol consumption and daily smoking. Results. Cancer was diagnosed in 36 homozygotes, five of which had two cancer diagnoses. The overall cancer incidence was not increased in C282Y homozygotes (hazard ratio 1.10 [95% CI 0.60–2.03] in women and 0.94 [95% CI 0.53–1.66] in men). However, homozygous men had increased risk of colorectal cancer (hazard ratio 3.03 [95% CI 1.17–7.82], p = 0.022) and primary liver cancer (hazard ratio 54.0 [95% CI 2.68–1089], p = 0.009). The risk of breast cancer in homozygous women was not increased (hazard ratio 1.13 [95% CI 0.35–3.72]). Adjusted for other variables including C282Y homozygosity, very low and very high serum transferrin saturation were associated with increased overall cancer incidence. Conclusions. C282Y homozygosity is associated with increased risk of colorectal cancer and hepatocellular cancer in men. In the general population, individuals with a very low or a very high serum transferrin saturation may have increased cancer risk.

Key Words::

• breast cancer
• colorectal cancer
• hazard models
• hemochromatosis
• hepatocellular cancer

Acknowledgements

The Nord-Trøndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine, Norwegian University of Science and Technology NTNU), Nord-Trøndelag County Council, Central Norway Health Authority, and the Norwegian Institute of Public Health. This work was also supported by Norwegian Haemochromatosis Association.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.