Correspondence to: Nicholas J. Shaheen, M.D., M.P.H., University of North Carolina, CB#7080, Chapel Hill, NC 275997080 (e-mail: nshaheen{at}med.unc.edu).
Dr. Sullivan points out an interesting and plausible source of bias in our study (1). Subjects with colon cancer often present with iron deficiency anemia. If subjects with an HFE gene mutation have higher iron stores on average than subjects without HFE gene mutations, subjects with HFE gene mutation would present with more advanced stages of colon cancer because of the delayed onset of iron deficiency. If subjects with HFE gene mutations and very advanced cancers died before they could be included in our study, their differential loss would skew our results. As Dr. Sullivan notes, this bias, if it existed, might have caused us to underestimate the strength of the association between colon cancer and HFE gene mutations.
We, too, were concerned that subjects with HFE mutations who developed cancer might present with more advanced or inoperable stages of disease. Because our study included both those with operable and inoperable cancers, this was a testable hypothesis. We compared the tumor stages at diagnosis (classified as in situ, local, regional, or distant) of subjects who had an HFE mutation with those who did not. We found no statistically significant differences in tumor stage at diagnosis, based on HFE gene mutation status. We also asked whether those with HFE gene mutations had different symptoms at presentation than those without such mutations. Again, no statistically significant differences were noted.
Given these results, it is unlikely that we substantially underestimated the association between HFE gene mutations and colon cancer because of this potential bias. Moreover, we minimized the time between diagnosis and enrollment into the study by use of the rapid ascertainment system of the North Carolina Cancer Registry: study subjects were identified at a median of 34 days after their diagnosis. Thus, even in subjects presenting with very advanced disease, this period of time seems unlikely to allow for loss of a substantial number of participants due to death from cancer.
Although we agree with Dr. Sullivan that limiting iron intake to lower cancer risk may not be unreasonable conceptually, it may not be prudent to limit dietary iron intake until studies demonstrate that such measures are effective. Dietary changes to avoid intake of iron, if done in an unsupervised way, could promote less healthy eating in general, which might increase the individuals risk of other conditions, such as heart disease. However, as more data emerge regarding the effects of iron stores on the risk of disease, long-standing practices, such as the fortification of foods with iron and the routine addition of iron to multivitamins, should be revisited. It is likely that the "right" amount of iron will differ from individual to individual, and our current "one-size-fits-all" approach will need tailoring to fit our developing understanding of the role of iron in disease.
REFERENCES
1 Shaheen NJ, Silverman LM, Keku T, Lawrence LB, Rohlfs EM, Martin CF, et al. Association between hemochromatosis (HFE) gene mutation carrier status and the risk of colon cancer. J Natl Cancer Inst 2003;95:1549.
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |