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Positive and Negative Associations of Human Leukocyte Antigen Variants with the Onset and Prognosis of Adult Glioblastoma Multiforme

Departments of ¹ Medicine, ² Epidemiology, and ³ Surgery, University of Alabama at Birmingham, Birmingham, Alabama; and ⁴ Department of Neurological Surgery, University of California, San Francisco, California

Request for reprints: Richard A. Kaslow, Program in Epidemiology of Infection and Immunity, Schools of Medicine and Public Health, University of Alabama at Birmingham, 1665 University Boulevard, RPHB Room 220A, Birmingham, AL 35294-0022. Phone: 205-975-8698; Fax: 205-934-8665. E-mail: rkaslow{at}uab.edu

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.

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