altered iron metabolism / aggressive breast cancer



Cancer Epidemiol Biomarkers Prev. 2004 Feb 1;13(2):205-212. Related Articles, Links

Increased Prevalence of the HFE C282Y Hemochromatosis Allele in Women with Breast Cancer.

Kallianpur AR, Hall LD, Yadav M, Christman BW, Dittus RS, Haines JL, Parl FF, Summar ML.

Department of Medicine, Division of General Internal Medicine, Department of Pediatrics, Division of
Medical Genetics, Department of Medicine, Division of Allergy, Pulmonary, and Critical Care
Medicine, Center for Health Services Research, Department of Molecular Physiology and Biophysics,
and Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, and VA
Center for Health Services Research and Tennessee Valley Geriatric and Education Clinical Center and
Quality Scholars Program, Veterans Affairs Medical Center, Nashville, Tennessee.

Individuals with the major hemochromatosis (HFE) allele C282Y and iron overload develop
hepatocellular and some extrahepatic malignancies at increased rates. No association has been
previously reported between the C282Y allele and breast cancer. We hypothesized that due to the pro-
oxidant properties of iron, altered iron metabolism in C282Y carriers may promote breast
carcinogenesis. Because 1 in 10 Caucasians of Northern European ancestry carries this allele, any
impact it may have on breast cancer burden is potentially great. We determined C282Y genotypes in
168 patients who underwent high-dose chemotherapy and blood cell transplantation for cancer: 41 with
breast cancer and 127 with predominantly hematological cancers (transplant cohort). Demographic,
clinical, and tumor characteristics were reviewed in breast cancer patients. The frequency of C282Y
genotypes in breast cancers was compared with the frequency in nonbreast cancers, an outpatient
sample from Tennessee (n = 169), and a published United States national sample. The frequency of at
least one C282Y allele in breast cancers was higher (36.6%, 5 homozygotes/10 heterozygotes) than
frequencies in Tennessee (12.7%, P < 0.001), the general population (12.4%, P < 0.001), and
similarly selected nonbreast cancers (17.0%, P = 0.008). The likelihood of breast cancer in the
transplant cohort increased with C282Y allele dose (P(trend) = 0.010). These results were supported
by the finding in a nontransplant cohort of a higher frequency of C282Y mutations in Caucasian
(18.4%, P = 0.039) and African-American (8.5%, P = 0.005) women with breast cancer than race-
specific national frequency estimates. A high prevalence of C282Y alleles in women with
breast cancer with and without poor risk features suggests that altered iron metabolism in
C282Y carriers may promote the development of breast cancer and/or more aggressive forms of
the disease.

PMID: 14973098 [PubMed - as supplied by publisher]


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