title: Positive and negative associations of human leukocyte antigen variants with the onset and prognosis of adult glioblastoma multiforme.
abstract: Associations of genetic factors with malignant gliomas have been modest. We examined the relationships of human leukocyte antigen (HLA) and related polymorphisms to glioblastoma multiforme in adult Caucasians (non-Hispanic Whites) from the San Francisco Bay area. For 155 glioblastoma multiforme patients and 157 control subjects closely matched by ethnicity, age, and gender, PCR-based techniques resolved alleles at HLA-A, -B, -C, and -DRB1 loci along with short tandem repeat polymorphisms of MICA exon 5 and TNFb. By multivariable logistic regression, B*13 and the B*07-Cw*07 haplotype were positively associated with glioblastoma multiforme (P=0.01 and <0.001, respectively), whereas Cw*01 was the only variant showing a negative association (P=0.05). Among glioblastoma multiforme patients, progression to death after diagnosis was slower in those with A*32 (relative hazard, 0.45; P<0.01) and faster in those with B*55 (relative hazard, 2.27; P<0.01). Thus, both the occurrence and the prognosis of glioblastoma multiforme could be associated with specific but different HLA genotypes. B*07 and the B*07-Cw*07 haplotype are much more common in Caucasians than other ethnic groups in the U.S., which may partially explain the higher incidence of glioblastoma multiforme in Caucasians.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 1665 University Boulevard, RPHB Room 220A, Birmingham, AL 35294-0022, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Wenshuo
authors.initials: W
authors.lastname: Shao
authors.forename: M Tevfik
authors.initials: MT
authors.lastname: Dorak
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.forename: Rei
authors.initials: R
authors.lastname: Miike
authors.forename: Elena
authors.initials: E
authors.lastname: Lobashevsky
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.forename: Margaret
authors.initials: M
authors.lastname: Wrensch
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cobbs
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D012495:San Francisco
chemical_list: D014408:Biomarkers, Tumor; D006680:HLA Antigens