title: HFE polymorphisms affect survival of brain tumor patients.
abstract: The HFE (high iron) protein plays a key role in the regulation of body iron. HFE polymorphisms (H63D and C282Y) are the common genetic variants in Caucasians. Based on frequency data, both HFE polymorphisms have been associated with increased risk in a number of cancers. The prevalence of the two major HFE polymorphisms in a human brain tumor patient populations and the impact of HFE polymorphisms on survival have not been studied. In the present study, there is no overall difference in survival by HFE genotype. However, male GBM patients with H63D HFE (H63D) have poorer overall survival than wild type HFE (WT) male GBM (p = 0.03). In GBM patients with the C282Y HFE polymorphism (C282Y), female patients have poorer survival than male patients (p = 0.05). In addition, female metastatic brain tumor patients with C282Y have shorter survival times post diagnosis than WT patients (p = 0.02) or male metastatic brain tumor patients with C282Y (p = 0.02). There is a tendency toward a lower proportion of H63D genotype in GBM patients than a non-tumor control group (p = 0.09) or other subtypes of brain tumors. In conclusion, our study suggests that HFE genotype impacts survival of brain tumor patients in a gender specific manner. We previously reported that glioma and neuroblastoma cell lines with HFE polymorphisms show greater resistance to chemo and radiotherapy. Taken together, these data suggest HFE genotype is an important consideration for evaluating and planning therapeutic strategies in brain tumor patients.
authors.affiliation: Department of Neurosurgery, H110, The Pennsylvania State University College of Medicine, Penn State Hershey Medical Center, Penn State Hershey Cancer Institute, 500 University Drive (H110), Hershey, PA, 17033-0850, USA, SYL3@psu.edu.
authors.forename: Sang Y
authors.initials: SY
authors.lastname: Lee
authors.forename: Becky
authors.initials: B
authors.lastname: Slagle-Webb
authors.forename: Jonas M
authors.initials: JM
authors.lastname: Sheehan
authors.forename: Junjia
authors.initials: J
authors.lastname: Zhu
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Muscat
authors.forename: Michael
authors.initials: M
authors.lastname: Glantz
authors.forename: James R
authors.initials: JR
authors.lastname: Connor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins