title: Investigation of genetic variants of genes of the hemochromatosis pathway and their role in breast cancer.
abstract: Iron overload has been noticed as a feature of human breast cancer. Cellular iron uptake is regulated by the hemochromatosis and transferrin receptor system, mutations of which cause the iron storage disease hereditary hemochromatosis. To understand the role of hemochromatosis and transferrin receptor system mutations in breast cancer, we analyzed 19 sequence variations at HFE, TFR1, TFR2, and FPN1 and compared genotype frequencies between cases and controls in a German population. There were 688 breast cancer patients and 724 population-based and age-matched controls. For genotyping, we applied the Hemochromatosis Strip Assay and TaqMan allelic discrimination analyses. In addition to genotype frequencies, we established frequencies of compound genotypes. The frequencies of HFE at His63Asp, Ser65Cys, and Cys282Tyr, and of TFR1 at Ser142Gly minor alleles in this German population were 15.9%, 1.8%, 5.6%, and 46.0%, respectively. No rare variants at 15 more loci at HFE, TFR2, and FPN1 were observed in breast cancer patients. There were no significant differences of allele and genotype frequencies between cases and controls. Triple and quadruple compound genotypes at HFE_His63_Cys282-TFR1_Ser142Gly and HFE_His63_Ser65_Cys282-TFR1_Ser142Gly showed a nonsignificant increase in cases. Although limited by low numbers, an increased prevalence of the HFE Tyr282 minor allele was observed in breast cancer cases with a high number of affected lymph nodes (P = 0.032). Our data suggest that variants of the hemochromatosis-transferrin receptor system have no direct effect on the incidence of breast cancer in Germany. Possible effects on tumor progression and prognosis remain elusive.
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbachstrasse 112, D-70376 Stuttgart, Germany.
authors.forename: Benny K
authors.initials: BK
authors.lastname: Abraham
authors.forename: Christina
authors.initials: C
authors.lastname: Justenhoven
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Volker
authors.initials: V
authors.lastname: Harth
authors.forename: Gregor
authors.initials: G
authors.lastname: Weirich
authors.forename: Christian
authors.initials: C
authors.lastname: Baisch
authors.forename: Sylvia
authors.initials: S
authors.lastname: Rabstein
authors.forename: Yon-Dschun
authors.initials: YD
authors.lastname: Ko
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Fischer
authors.forename: Susanne
authors.initials: S
authors.lastname: Haas
authors.forename: Sandra
authors.initials: S
authors.lastname: Brod
authors.forename: Christian
authors.initials: C
authors.lastname: Oberkanins
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Brauch
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006432:Hemochromatosis / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007501:Iron / Q000378:metabolism; D016015:Logistic Models; D008593:Menopause; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D007501:Iron