| Adult glioma is a lethal primary brain tumor that demonstrates familial aggregation and ethnic differences. A genetic polymorphism study using a whole-genome approach could elucidate the genetic basis of adult glioma and is therefore important for risk assessment. A meta-analysis of 2 genome-wide association studies (GWAS) has identified a five globally significant glioma risk loci, including 5p15.33 (TERT), 8q24.21 (CCDC26 ), 9p21.3 (CDKN2A/p14(ARF)/CDKN2B), 11q23.3 ( PHLDB1), and 20q13.33 (RTEL1). We hypothesized that some of these disease-specific alleles also contribute to the familial aggregation observed in the Caucasian population. We examined a subset of 1,229 U.S. and Canadian Caucasian glioma patients from above-mentioned meta-analysis using a case-only design to detect correlations between the top 122 SNPs identified and family history of brain tumors and cancers other than brain tumors. 1q24.2 (UCK2), 1q24.2 (PRELP), 6q14.1 ( IBTK), 12p12.1 (SOX5), and 13q14.3 (DLEU7 ) were associated with brain tumor aggregation and 2p23.3 ( DNMT3A), 6q26 (PARK2), and 17q22 (RPL7P48 ) were linked to the aggregation of non-brain tumor cancers. Among the top 5 loci identified in the previous case-control study, none was associated with brain tumor risk, and the only SNP rs4977756 at 9p21.3 was significantly associated with elevated non-brain tumor cancer risk among the patients' first-degree relatives. Our data warrant further investigation of the role of these loci in the risk of familial aggregation of cancer and ethnic differences. |
