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Genetic variations in the homologous recombination repair pathway genes modify risk of glioma

  • Laboratory Investigation
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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.

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Acknowledgments

China National “211” Environmental Genomics Grant. We thank the participants and staffs at the Huashan Hospital of Fudan University whose help made this study possible. Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200433, China

    Haishi Zhang, Keke Zhou, Chengcheng Zhou & Liangfu Zhou

  2. Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Yanhong Liu, Renke Zhou & Chunxia Cheng

  3. Department of Obstetrics and Gynecology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China

    Chunxia Cheng

  4. Duke Cancer Institute, Duke University School of Medicine, Durham, NC, 27710, USA

    Qingyi Wei

  5. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, No. 220 Handan Road, Shanghai, 200433, China

    Daru Lu

  6. Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai, 200040, China

    Liangfu Zhou

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  1. Haishi Zhang
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  2. Yanhong Liu
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  3. Keke Zhou
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  4. Chengcheng Zhou
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  7. Qingyi Wei
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  8. Daru Lu
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  9. Liangfu Zhou
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Corresponding authors

Correspondence to Daru Lu or Liangfu Zhou.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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All of the authors have declared no conflicts of interest.

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Zhang, H., Liu, Y., Zhou, K. et al. Genetic variations in the homologous recombination repair pathway genes modify risk of glioma. J Neurooncol 126, 11–17 (2016). https://doi.org/10.1007/s11060-015-1892-0

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  • DOI: https://doi.org/10.1007/s11060-015-1892-0

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