title: Genetic variations in the homologous recombination repair pathway genes modify risk of glioma.
abstract: Accumulative epidemiological evidence suggests that single nucleotide polymorphisms (SNPs) in genes involved in homologous recombination (HR) DNA repair pathway play an important role in glioma susceptibility. However, the effects of such SNPs on glioma risk remain unclear. We used a used a candidate pathway-based approach to elucidate the relationship between glioma risk and 12 putative functional SNPs in genes involved in the HR pathway. Genotyping was conducted on 771 histologically-confirmed glioma patients and 752 cancer-free controls from the Chinese Han population. Odds ratios (OR) were calculated both for each SNP individually and for grouped analyses, examining the effects of the numbers of adverse alleles on glioma risk, and evaluated their potential gene-gene interactions using the multifactor dimensionality reduction (MDR). In the single-locus analysis, two variants, the NBS1 rs1805794 (OR 1.42, 95% CI 1.15-1.76, P = 0.001), and RAD54L rs1048771 (OR 1.61, 95% CI 1.17-2.22, P = 0.002) were significantly associated with glioma risk. When we examined the joint effects of the risk-conferring alleles of these three SNPs, we found a significant trend indicating that the risk increases as the number of adverse alleles increase (P = 0.005). Moreover, the MDR analysis suggested a significant three-locus interaction model involving NBS1 rs1805794, MRE11 rs10831234, and ATM rs227062. These results suggested that these variants of the genes involved in the HR pathway may contribute to glioma susceptibility.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200433, China.
authors.forename: Haishi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200433, China.
authors.forename: Keke
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200433, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Renke
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.|Department of Obstetrics and Gynecology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Duke Cancer Institute, Duke University School of Medicine, Durham, NC, 27710, USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, No. 220 Handan Road, Shanghai, 200433, China. drlu@fudan.edu.cn.
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200433, China. lfzhouc@online.sh.cn.|Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai, 200040, China. lfzhouc@online.sh.cn.
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D059767:Recombinational DNA Repair / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D055815:Young Adult
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins
keywords: Functional polymorphism; Glioma; Homologous recombination pathway; Susceptibility