HFE gene mutations in leukemia:: HuGE review susceptibility to childhood

被引:26
作者
Dorak, MT
Burnett, AK
Worwood, M
机构
[1] Newcastle Univ, Sch Clin Med Sci, Sir James Spence Inst Child Hlth, Royal Victoria Infirm, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[2] Cardiff Univ, Dept Haematol, Sch Med, Wales Coll Med, Cardiff CF4 4XN, S Glam, Wales
关键词
HFE gene polymorphism; hereditary hemochromatosis; leukemia; Hodgkin disease; cancer; epidemiology;
D O I
10.1097/01.GIM.0000156532.04648.81
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The hereditary hemochromatosis (HHC) gene, HFE on chromosome 6p21.3, encodes a protein involved in iron homeostasis. HFE mutations have low penetrance with a mild effect on serum iron levels. Animal, twin, and population studies have shown that carrier state for C282Y can increase iron levels. A proportion of heterozygotes show slightly elevated serum iron levels. Increased serum iron has been suggested to increase the risk for oxidative damage to DNA. Epidemiologic studies established a correlation between iron levels and cancer risk. Case-control studies have reported associations between HFE mutations C282Y/H63D and several cancers, some of which in interaction with the transferrin receptor gene TFRC or dietary iron intake. Increased cancer risk in C282Y carriers is likely due to higher iron levels in a multifactorial setting. In childhood acute lymphoblastic leukemia (ALL), there is an association of C282Y with a gender effect in two British populations. No association has been found in acute myeloblastic leukemia and Hodgkin disease in adults. The childhood leukemia association possibly results from elevated intracellular iron in lymphoid cells increasing the vulnerability to DNA damage at a critical time window during lymphoid cell development. Interactions of HFE with environmental and genetic factors, most of which are recognized, may play a role in modification of susceptibility to leukemia conferred by C282Y. Given the population frequency of C282Y and the connection between iron and cancer, clarification of the mechanism of HFE associations in leukemia and cancer will have strong implications in public health.
引用
收藏
页码:159 / 168
页数:10
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