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Genetic variants in N-myc (and STAT) interactor and susceptibility to glioma in a Chinese Han population

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Tumor Biology

Abstract

Glioma is one of the most common and lethal brain tumors. N-myc (and STAT) interactor (NMI) gene has been reported in tumorigenesis, and our previous study further showed its implication in glioma progression. To elucidate its involvement in the etiology of glioma, we conducted a case–control study of 875 patients and 1040 controls in a Chinese Han population by genotyping 7 representative single nucleotide polymorphisms (SNPs) in NMI. Allele and genotype frequency distribution of five loci (rs2278089, rs2194492, rs6734376, rs3854012, and rs11730) were significantly different between the cases and controls. Unconditional logistic regression showed that the variant genotypes of rs2278089 [adjusted odds ratio (OR) = 1.57, P = 4.23 × 10−6], rs2194492 (adjusted OR = 1.49, P = 1.20 × 10−4), and rs6734376 (adjusted OR = 0.06, P = 8.65 × 10−13) significantly affected glioma risk compared with the major homozygotes, while the minor homozygotes of rs3854012 (adjusted OR = 0.54, P = 4.64 × 10−6) and rs11730 (adjusted OR = 0.60, P = 1.50 × 10−4) showed significant protective effects. Further stratified analyses indicated that these associations remained significant in subgroups of low-grade glioma (LGG) and high-grade glioma (HGG). Additionally, haplotype and diplotype analyses showed consistent results. The Bonferroni correction was applied for all these analyses. Moreover, luciferase reporter gene assays revealed enhanced promoter activity of the C risk allele of rs2194492 in several cell lines compared with the G major allele, suggesting its potential function in transcriptional activation of NMI. Taken together, these results revealed that NMI polymorphisms may contribute to genetic susceptibility to glioma.

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Acknowledgments

We thank all staff of the Department of Neurosurgery of Huashan Hospital for their help of sample and epidemiology data collection. We also thank all volunteers recruited in this study for their help of DNA preparing. This work was supported by the National Natural Science Foundation of China (grants 81372706, 81372235, 81170786, and 81071739).

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Authors and Affiliations

  1. State Key Laboratory of Genetic Engineering, Fudan-VARI Genetic Epidemiology Center and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, No. 2005 Songhu Road, Shanghai, 200438, People’s Republic of China

    Delong Meng, Xiaoying Li, Shuo Zhang, Yingjie Zhao, Xiao Song, Yuanyuan Chen, Shiming Wang, Hongyan Chen & Daru Lu

  2. Department of Neurosurgery, Huashan Hospital, Fudan University, No. 12 Wulumuqi Zhong Rd, Shanghai, 200040, People’s Republic of China

    Ying Mao

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  1. Delong Meng
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  2. Xiaoying Li
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Correspondence to Ying Mao or Hongyan Chen.

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Meng, D., Li, X., Zhang, S. et al. Genetic variants in N-myc (and STAT) interactor and susceptibility to glioma in a Chinese Han population. Tumor Biol. 36, 1579–1588 (2015). https://doi.org/10.1007/s13277-014-2745-8

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  • DOI: https://doi.org/10.1007/s13277-014-2745-8

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