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

Journal of Neuro-Oncology volume 105, pages 211–218 (2011)Cite this article

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.

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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

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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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Affiliations

  1. State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes for Biomedical Sciences, Fudan University, 220 Handan Rd, Shanghai, China

    Weiwei Fan, Yingjie Zhao, Wenting Wu, Hongyan Chen, Li Jin & Daru Lu

  2. Neurosurgery Department of Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Rd, Shanghai, China

    Keke Zhou, Gong Chen, Jinlong Shi, Guhong Du, Ying Mao & Liangfu Zhou

  3. Neurosurgery Department of Shanghai Puto District People’s Hospital, Shanghai, China

    Keke Zhou

  4. Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Qingyi Wei

  5. Department of Health Toxicology, College of Basic Medical Sciences, Second Military Medical University, Shanghai, China

    Tianbao Zhang

Authors
  1. Weiwei Fan
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  2. Keke Zhou
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  3. Yingjie Zhao
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  4. Wenting Wu
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  5. Hongyan Chen
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  6. Li Jin
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  7. Gong Chen
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  8. Jinlong Shi
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  9. Qingyi Wei
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  10. Tianbao Zhang
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  11. Guhong Du
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  12. Ying Mao
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  13. Daru Lu
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  14. Liangfu Zhou
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Corresponding authors

Correspondence to Ying Mao or Daru Lu.

Additional information

Weiwei Fan and Keke Zhou contributed equally to this study.

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Fan, W., Zhou, K., Zhao, Y. et al. Possible association between genetic variants in the H2AFX promoter region and risk of adult glioma in a Chinese Han population. J Neurooncol 105, 211–218 (2011). https://doi.org/10.1007/s11060-011-0586-5

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  • DOI: https://doi.org/10.1007/s11060-011-0586-5

Keywords

  • DNA repair
  • Glioma
  • H2AFX
  • Tagging SNP
  • Association study