Abstract
Background: Polymorphisms in the hemochromatosis (HFE) gene are associated with excessive iron absorption from the diet, and pro-oxidant effects of iron accumulation are thought to be a risk factor for several types of cancer. Methods: The C282Y (rs1800562) and H63D (rs1799945) polymorphisms were genotyped in 301 oral cancer cases and 437 controls and analyzed in relation to oral cancer risk, and serum iron biomarker levels from a subset of 130 subjects. Results: Individuals with the C282Y allele had lower total iron binding capacity (TIBC) (321.2 ± 37.2 µg/dL vs. 397.7 ± 89.0 µg/dL, p = 0.007) and higher percent transferrin saturation (22.0 ± 8.7 vs. 35.6 ± 22.9, p = 0.023) than wild type individuals. Iron and ferritin levels approached significantly higher levels for the C282Y allele (p = 0.0632 and p = 0.0588, respectively). Conclusions: Iron biomarker levels were elevated by the C282Y allele, but neither (rs1800562) nor (rs1799945) was associated with oral cancer risk in blacks and whites.
Highlights
The HFE gene produces a protein located on the surface of liver and intestinal cells that acts to detect iron levels
The mean pack-years of smoking for White and Black oral cancer cases (41.8 and 43.5 pack-years, respectively) was significantly (p < 0.01) higher than the mean pack-years observed for White and Black controls (17.6 and 18.4 pack-years, respectively)
HFE causes an increase in hepcidin levels by sensing when iron levels in the body are high, so a non-functional or reduced function variant of the HFE gene can lead to excessive absorption and an imbalance in iron homeostasis
Summary
The HFE gene produces a protein located on the surface of liver and intestinal cells that acts to detect iron levels. The C282Y polymorphism prevents the protein from reaching the cell surface, resulting in an inability to accurately sense iron levels in the body [1,2,3]. Individuals homozygous for this allele can display severe iron accumulation and are at 20-fold increased risk for hepatocellular carcinoma (HCC) [4] and several large-scale studies have identified the C282Y polymorphism as a risk factor for HCC [5,6]. Polymorphisms in the hemochromatosis (HFE) gene are associated with excessive iron absorption from the diet, and pro-oxidant effects of iron accumulation are thought to be a risk factor for several types of cancer. Conclusions: Iron biomarker levels were elevated by the C282Y allele, but neither (rs1800562) nor (rs1799945) was associated with oral cancer risk in blacks and whites.
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