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Associations between polymorphisms in DNA repair genes and glioblastoma.

Authors
McKean-Cowdin-R; Barnholtz-Sloan-J; Inskip-PD; Ruder-AM; Butler-M; Rajaraman-P; Razavi-P; Patoka-J; Wiencke-JK; Bondy-ML; Wrensch-M
Source
Cancer Epidemiol Biomark Prev 2009 Apr; 18(4):1118-1126
NIOSHTIC No.
20035207
Abstract
A pooled analysis was conducted to examine the association between select variants in DNA repair genes and glioblastoma multiforme, the most common and deadliest form of adult brain tumors. Genetic data for approximately 1,000 glioblastoma multiforme cases and 2,000 controls were combined from four centers in the United States that have conducted case-control studies on adult glioblastoma multiforme, including the National Cancer Institute, the National Institute for Occupational Safety and Health, the University of Texas M. D. Anderson Cancer Center, and the University of California at San Francisco. Twelve DNA repair single-nucleotide polymorphisms were selected for investigation in the pilot collaborative project. The C allele of the PARP1 rs1136410 variant was associated with a 20% reduction in risk for glioblastoma multiforme (odds ratioCT or CC, 0.80; 95% confidence interval, 0.67-0.95). A 44% increase in risk for glioblastoma multiforme was found for individuals homozygous for the G allele of the PRKDC rs7003908 variant (odds ratioGG, 1.44; 95% confidence interval, 1.13-1.84); there was a statistically significant trend (P = 0.009) with increasing number of G alleles. A significant, protective effect was found when three single-nucleotide polymorphisms (ERCC2 rs13181, ERCC1 rs3212986, and GLTSCR1 rs1035938) located near each other on chromosome 19 were modeled as a haplotype. The most common haplotype (AGC) was associated with a 23% reduction in risk (P = 0.03) compared with all other haplotypes combined. Few studies have reported on the associations between variants in DNA repair genes and brain tumors, and few specifically have examined their impact on glioblastoma multiforme. Our results suggest that common variation in DNA repair genes may be associated with risk for glioblastoma multiforme.
Keywords
Genes; Genetics; DNA-damage; Central-nervous-system-disorders; Brain-disorders; Cancer; Cancer-rates; Epidemiology; Statistical-analysis; Author Keywords: DNA repair; glioblastoma; brain tumor; polymorphisms; pooled
Contact
Roberta McKean-Cowdin, University of Southern California/Norris Cancer Center, Mailstop/44 Room 4419, 1441 Eastlake Avenue, Los Angeles, CA 90033
CODEN
CEBPE4
Publication Date
20090401
Document Type
Journal Article
Email Address
mckeanco@usc.edu
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Issue of Publication
4
ISSN
1055-9965
NIOSH Division
DSHEFS; DART
Priority Area
Agriculture, Forestry and Fishing; Manufacturing
Source Name
Cancer Epidemiology, Biomarkers & Prevention
State
CA; OH; MD; TX
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