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Comprehensive Analysis of DNA Repair Gene Variants and Risk of Meningioma.

Authors :
Bethke, Lara
Murray, Anne
Webb, Emily
Schoemaker, Minouk
Muir, Kenneth
McKinney, Patricia
Hepworth, Sarah
Dimitropoulou, Polyxeni
Lophatananon, Artitaya
Feychting, Maria
Lönn, Stefan
Ahlbom, Anders
Malmer, Beatrice
Henriksson, Roger
Auvinen, Anssi
Kiuru, Anne
Salminen, Tiina
Johansen, Christoffer
Christensen, Helle Collatz
Kosteljanetz, Michael
Source :
JNCI: Journal of the National Cancer Institute; 2/20/2008, Vol. 100 Issue 4, p270-276, 7p, 4 Graphs
Publication Year :
2008

Abstract

Background Meningiomas account for up to 37% of all primary brain tumors. Genetic susceptibility to meningioma is well established, with the risk among relatives of meningioma patients being approximately threefold higher than that in the general population. A relationship between risk of meningioma and exposure to ionizing radiation is also well known and led us to examine whether variants in DNA repair genes contribute to disease susceptibility. Methods We analyzed 1127 tagging single-nucleotide polymorphisms (SNPs) that were selected to capture most of the common variation in 136 DNA repair genes in five case-control series (631 case patients and 637 control subjects) from four countries in Europe. We also analyzed 388 putative functional SNPs in these genes for their association with meningioma. All statistical tests were two-sided. Results The SNP rs4968451, which maps to intron 4 of the gene that encodes breast cancer susceptibility gene 1-interacting protein 1, was consistently associated with an increased risk of developing meningioma. Across the five studies, the association was highly statistically significant (trend odds ratio = 1.57, 95% confidence interval = 1.28 to 1.93; P<subscript>trend</subscript> = 8.95 × 10<superscript>-6</superscript>; P= .009 after adjusting for multiple testing). Conclusions We have identified a novel association between rs4968451 and meningioma risk. Because approximately 28% of the European population are carriers of at-risk genotypes for rs4968451, the variant is likely to make a substantial contribution to the development of meningioma. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00278874
Volume :
100
Issue :
4
Database :
Complementary Index
Journal :
JNCI: Journal of the National Cancer Institute
Publication Type :
Academic Journal
Accession number :
31205211
Full Text :
https://doi.org/10.1093/jnci/djn004