Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma

Yanhong Liu, Beatrice S. Melin, Preetha Rajaraman, Zhaoming Wang, Martha Linet, Sanjay Shete, Christopher I. Amos, Ching C. Lau, Michael E. Scheurer, Spiridon Tsavachidis, Georgina N. Armstrong, Richard S. Houlston, Fay J. Hosking, Elizabeth B. Claus, Jill Barnholtz-Sloan, Rose Lai, Dora Il'yasova, Joellen Schildkraut, Siegal Sadetzki, Christoffer JohansenJonine L. Bernstein, Sara H. Olson, Robert B. Jenkins, Daniel La Chance, Nicholas A. Vick, Margaret Wrensch, Faith Davis, Bridget J. McCarthy, Ulrika Andersson, Patricia A. Thompson, Stephen Chanock, Melissa L. Bondy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P trend <1.0 × 10 -8). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.

Original languageEnglish
Pages (from-to)1507-1517
Number of pages11
JournalHuman Genetics
Issue number9
StatePublished - Sep 2012


FundersFunder number
Tug McGraw Foundation
National Institutes of Health5R01 CA070917, R01CA52689
National Cancer InstituteR01CA119215
American Brain Tumor Association
National Brain Tumor Society
Wellcome Trust


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