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Journal of Neuro-Oncology

, Volume 105, Issue 2, pp 211–218 | Cite as

Possible association between genetic variants in the H2AFX promoter region and risk of adult glioma in a Chinese Han population

  • Weiwei Fan
  • Keke Zhou
  • Yingjie Zhao
  • Wenting Wu
  • Hongyan Chen
  • Li Jin
  • Gong Chen
  • Jinlong Shi
  • Qingyi Wei
  • Tianbao Zhang
  • Guhong Du
  • Ying MaoEmail author
  • Daru LuEmail author
  • Liangfu Zhou
Laboratory Investigation - Human/Animal Tissue

Abstract

H2AFX, a histone H2A gene family member X, is a key component in the detection of and response to DNA double-strand breaks (DSBs) caused by ionizing radiation (IR), a known risk factor for glioma. Thus, genetic variants in the H2AFX promoter region that may result in abnormal protein expression could confer susceptibility to glioma. In this case–control study, we genotyped three common single-nucleotide polymorphisms (SNPs) (rs643788, rs8551, and rs2509851) in the H2AFX promoter region in 669 adult glioma patients and 638 cancer-free controls. The associations between each SNP or haplotype and glioma risk were estimated by calculating odds ratios (ORs) and the corresponding 95% confidence interval (CI) using unconditional logistic regression models, with adjustment for age and sex. The H2AFX rs643788 A variant genotypes were significantly associated with reduced risk of glioma (GA versus GG: adjusted OR = 0.72, 95% CI = 0.56–0.94; GA/AA versus GG: adjusted OR = 0.75, 95% CI = 0.59–0.94), compared with the common GG genotype. Furthermore, this decreased risk was more evident among those aged ≥45 years (adjusted OR = 0.64, 95% CI = 0.45–0.90), male subjects (adjusted OR = 0.70, 95% CI = 0.50–0.96), and patients with glioblastoma (adjusted OR = 0.66, 95% CI = 0.46–0.94). These results suggest that a common variant in the H2AFX promoter region may modulate risk of glioma, particularly for adult glioma. However, our findings need to be replicated in other independent populations.

Keywords

DNA repair Glioma H2AFX Tagging SNP Association study 

Abbreviations

H2AFX

H2A histone family member X

IR

Ionizing radiation

OR

Odds ratio

CI

Confidence interval

DSB

Double-strand break

SNP

Single-nucleotide polymorphism

UTR

Untranslated region

LD

Linkage disequilibrium

MAF

Minimum allele frequency

HWE

Hardy–Weinberg equilibrium

DPAGT1

Dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1 (GlcNAc-1-P transferase)

GWA

Genome-wide association

CEU

90 Individuals (30 trios) in Utah, USA, from the Centre d’Etude du Polymorphisme Humain collection

CHB

45 Han Chinese in Beijing, China

Notes

Acknowledgments

The authors would like to thank Xilan Mei, Jian Yu, and Mei Chong for subject enrollment, Yin Wang and Wenting Wu for laboratory assistance, and Dr. Melissa Bondy for providing the M.D. Anderson brain tumor questionnaire. We also thank all participants of the Department of Neurosurgery of Huashan Hospital for their cooperation during data collection. This work was supported by Shanghai Science and Technology Research Program 09JC1402200, Shanghai Leading Scientist for Public Health 08GWD07, and Shanghai Key Subject Project for Public Health 08GWZX0301.

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Weiwei Fan
    • 1
  • Keke Zhou
    • 2
    • 3
  • Yingjie Zhao
    • 1
  • Wenting Wu
    • 1
  • Hongyan Chen
    • 1
  • Li Jin
    • 1
  • Gong Chen
    • 2
  • Jinlong Shi
    • 2
  • Qingyi Wei
    • 4
  • Tianbao Zhang
    • 5
  • Guhong Du
    • 2
  • Ying Mao
    • 2
    Email author
  • Daru Lu
    • 1
    Email author
  • Liangfu Zhou
    • 2
  1. 1.State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes for Biomedical SciencesFudan UniversityShanghaiChina
  2. 2.Neurosurgery Department of Huashan HospitalFudan UniversityShanghaiChina
  3. 3.Neurosurgery Department of Shanghai Puto District People’s HospitalShanghaiChina
  4. 4.Department of EpidemiologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  5. 5.Department of Health Toxicology, College of Basic Medical SciencesSecond Military Medical UniversityShanghaiChina

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