Molecular Epidemiology of Primary Brain Tumors

Abstract

Summary:Although primary brain tumors (PBTs) are generally considered to be a multifactorial disorder, understanding the genetic basis and etiology of the disease is essential for PBT risk assessment. Understanding of the genetic susceptibility for PBT has come from studies of rare genetic syndromes, linkage analysis, family aggregation, early-onset pediatric cases, and mutagen sensitivity. There are currently no effective markers to assess biological dose of exposures and genetic heterogeneity. The priorities recently recommended by the Brain Tumor Epidemiology Consortium emphasized the need for expanding research in genetics and molecular epidemiology. In this article, we review the literature to identify molecular epidemiologic case-control studies of PBTs that were hypothesis-driven and focused on four hypothesized candidate pathways: DNA repair, cell cycle, metabolism, and inflammation. We summarize the results in terms of genetic associations of single nucleotide polymorphisms of these pathways. We also discuss future research directions based on available evidence and technologies, and conclude that high resolution whole genome approach with significantly large sample size could rapidly advance our understanding of the genetic etiology of PBTs. Literature searches were done on PubMed in March 2009 with the terms glioma, glioblastoma, brain tumor, association, and polymorphism, and we only reviewed English language publications.

Cyclin D1 Gene G870A Variants and Primary Brain Tumors

“…A number of genetic syndromes have been confirmed as risk factors for brain cancer. At least three of these familial syndromes; retinoblastoma, neurofibromatosis and LiFraumeni syndrome are related with germ line mutations affecting cell cycle regulation and apoptosis (Inskip et al, 1995;Wrensch et al, 2002;Schwartzbaum et al, 2006;Rajaraman et al, 2007;Gu et al, 2009). …”

“…CX3CR1 (chemokine receptor 1 gene), CASP8 and CDKN2A (cyclin-dependent kinase inhibitor 2A) was reported to be associated with glioma risk (Gu et al, 2009). Frequent mutations or loss of expression of cell cycle control genes such as MDM2, NF1 and RB, also indicates the importance of cell cycle control in brain tumor formation (Holland, 2001;Rajaraman et al, 2007).…”

Association of the CCDC26 rs4295627 polymorphism with the risk of glioma: Evidence from 7,290 cases and 11,630 controls

“…However, the risk factors for glioma remain largely unknown. Gene susceptibility for glioma has been suggested in numerous case-control studies (18). The majority of studies conducted to date have evaluated a number of polymorphisms in a certain pathway, such as those affecting methylation, carcinogen metabolism, DNA repair, cell cycle, or inflammation.…”

Genomic Abnormalities in Gliomas

“…However, the ethnic variations, methodological variations, and the presence of responsible, functionally unknown SNPs in linkage disequilibrium with those SNPs analyzed have contributed to the dissemination of conflicting results in different parts of the world. Gu et al (2009) presented a review including a list of eight literature-defined, putative, functional, SNPs associated with gliomas in at least two populations from casecontrol studies. A summary of this list is presented in Table 3.…”