title: Analysis of single nucleotide variants of HFE gene and association to survival in The Cancer Genome Atlas GBM data.
abstract: Human hemochromatosis protein (HFE) is involved in iron metabolism. Two major HFE polymorphisms, H63D and C282Y, have been associated with an increased risk of cancers. Previously, we reported decreased gender effects in overall survival based on H63D or C282Y HFE polymorphisms patients with glioblastoma multiforme (GBM). However, the effect of other single nucleotide variation (SNV) in the HFE gene on the cancer development and progression has not been systematically studied. To expand our finding in a larger sample, and to identify other HFE SNV, we analyzed the frequency of somatic SNV in HFE gene and its relationship to survival in GBM patients using The Cancer Genome Atlas (TCGA) GBM (Caucasian only) database. We found 9 SNVs with increased frequency in blood normal of TCGA GBM patients compared to the 1000Genome. Among 9 SNVs, 7 SNVs were located in the intron and 2 SNVs (i.e., H63D, C282Y) in the exon of HFE gene. The statistical analysis demonstrated that blood normal samples of TCGA GBM have more H63D (p = 0.0002, 95% Confidence interval (CI): 0.2119-0.3223) or C282Y (p = 0.0129, 95% CI: 0.0474-0.1159) HFE polymorphisms than 1000Genome. The Kaplan-Meier survival curve for the 264 GBM samples revealed no difference between wild type (WT) HFE and H63D, and WT HFE and C282Y GBM patients. In addition, there was no difference in the survival of male/female GBM patients based on HFE genotype. There was no correlation between HFE expression and survival. In conclusion, the current results suggest that somatic HFE polymorphisms do not impact GBM patients' survival in the TCGA data set of GBM.
authors.affiliation: Department of Neurosurgery, The Pennsylvania State University College of Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania, United States of America.
authors.forename: Sang Y
authors.identifier: http://orcid.org/0000-0003-3911-8316
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Public Health Sciences, The Pennsylvania State University College of Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania, United States of America.
authors.forename: Junjia
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania, United States of America.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Salzberg
authors.affiliation: Department of Biochemistry & Molecular Biology, The Pennsylvania State University College of Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Public Health Sciences and Biochemistry & Molecular Biology, Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania, United States of America.
authors.forename: Dajiang J
authors.initials: DJ
authors.lastname: Liu
authors.affiliation: Department of Public Health Sciences, The Pennsylvania State University College of Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania, United States of America.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Muscat
authors.affiliation: Department of Neurosurgery, The Pennsylvania State University College of Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania, United States of America.
authors.forename: Sara T
authors.initials: ST
authors.lastname: Langan
authors.affiliation: Department of Neurosurgery, The Pennsylvania State University College of Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania, United States of America.
authors.forename: James R
authors.initials: JR
authors.lastname: Connor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality; D006432:Hemochromatosis / Q000235:genetics* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult