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01-11-2011 | Laboratory Investigation - Human/Animal Tissue

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

Authors: Weiwei Fan, Keke Zhou, Yingjie Zhao, Wenting Wu, Hongyan Chen, Li Jin, Gong Chen, Jinlong Shi, Qingyi Wei, Tianbao Zhang, Guhong Du, Ying Mao, Daru Lu, Liangfu Zhou

Published in: Journal of Neuro-Oncology | Issue 2/2011

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.

Xue QC, Pu PY, Yang YS, Shen CH (1990) A survey of 790 cases of astrocytoma. Clin Neurol Neurosurg 92:27–33PubMedCrossRef

Ohgaki H, Kleihues P (2005) Epidemiology and etiology of gliomas. Acta Neuropathol 109:93–108PubMedCrossRef

Bondy ML, Scheurer ME, Malmer B, Barnholtz-Sloan JS, Davis FG, Il’yasova D, Kruchko C, McCarthy BJ, Rajaraman P, Schwartzbaum JA, Sadetzki S, Schlehofer B, Tihan T, Wiemels JL, Wrensch M, Buffler PA (2008) Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium. Cancer 113:1953–1968PubMedCrossRef

Melean G, Sestini R, Ammannati F, Papi L (2004) Genetic insights into familial tumors of the nervous system. Am J Med Genet C Semin Med Genet 129C:74–84PubMedCrossRef

Sadetzki S, Chetrit A, Freedman L, Stovall M, Modan B, Novikov I (2005) Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for Tinea capitis. Radiat Res 163:424–432PubMedCrossRef

Malmer B, Adatto P, Armstrong G, Barnholtz-Sloan J, Bernstein JL, Claus E, Davis F, Houlston R, Il’yasova D, Jenkins R, Johansen C, Lai R, Lau C, McCarthy B, Nielsen H, Olson SH, Sadetzki S, Shete S, Wiklund F, Wrensch M, Yang P, Bondy M (2007) GLIOGENE an International Consortium to Understand Familial Glioma. Cancer Epidemiol Biomark Prev 16:1730–1734CrossRef

Dickey JS, Redon CE, Nakamura AJ, Baird BJ, Sedelnikova OA, Bonner WM (2009) H2AX: functional roles and potential applications. Chromosoma 118:683–692PubMedCrossRef

Bassing CH, Chua KF, Sekiguchi J, Suh H, Whitlow SR, Fleming JC, Monroe BC, Ciccone DN, Yan C, Vlasakova K, Livingston DM, Ferguson DO, Scully R, Alt FW (2002) Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX. Proc Natl Acad Sci USA 99:8173–8178PubMedCrossRef

Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA, Reina-San-Martin B, Coppola V, Meffre E, Difilippantonio MJ, Redon C, Pilch DR, Olaru A, Eckhaus M, Camerini-Otero RD, Tessarollo L, Livak F, Manova K, Bonner WM, Nussenzweig MC, Nussenzweig A (2002) Genomic instability in mice lacking histone H2AX. Science 296:922–927PubMedCrossRef

10.

Bassing CH, Suh H, Ferguson DO, Chua KF, Manis J, Eckersdorff M, Gleason M, Bronson R, Lee C, Alt FW (2003) Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Cell 114:359–370PubMedCrossRef

11.

Celeste A, Difilippantonio S, Difilippantonio MJ, Fernandez-Capetillo O, Pilch DR, Sedelnikova OA, Eckhaus M, Ried T, Bonner WM, Nussenzweig A (2003) H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 114:371–383PubMedCrossRef

12.

Celeste A, Fernandez-Capetillo O, Kruhlak MJ, Pilch DR, Staudt DW, Lee A, Bonner RF, Bonner WM, Nussenzweig A (2003) Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat Cell Biol 5:675–679PubMedCrossRef

13.

Monteiro AN, Zhang S, Phelan CM, Narod SA (2003) Absence of constitutional H2AX gene mutations in 101 hereditary breast cancer families. J Med Genet 40:e51PubMedCrossRef

14.

Walsh SH, Rosenquist R (2005) Absence of H2AX gene mutations in B-cell leukemias and lymphomas. Leukemia 19:464PubMedCrossRef

15.

Wilkie GS, Dickson KS, Gray NK (2003) Regulation of mRNA translation by 5′- and 3′-UTR-binding factors. Trends Biochem Sci 28:182–188PubMedCrossRef

16.

Buckland PR, Hoogendoorn B, Coleman SL, Guy CA, Smith SK, O’Donovan MC (2005) Strong bias in the location of functional promoter polymorphisms. Hum Mutat 26:214–223PubMedCrossRef

17.

Ponomarenko JV, Merkulova TI, Vasiliev GV, Levashova ZB, Orlova GV, Lavryushev SV, Fokin ON, Ponomarenko MP, Frolov AS, Sarai A (2001) rSNP_Guide, a database system for analysis of transcription factor binding to target sequences: application to SNPs and site-directed mutations. Nucleic Acids Res 29:312–316PubMedCrossRef

18.

Buckland PR (2006) The importance and identification of regulatory polymorphisms and their mechanisms of action. Biochim Biophys Acta 1762:17–28PubMed

19.

De Gobbi M, Viprakasit V, Hughes JR, Fisher C, Buckle VJ, Ayyub H, Gibbons RJ, Vernimmen D, Yoshinaga Y, de Jong P, Cheng JF, Rubin EM, Wood WG, Bowden D, Higgs DR (2006) A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter. Science 312:1215–1217PubMedCrossRef

20.

Novik KL, Spinelli JJ, Macarthur AC, Shumansky K, Sipahimalani P, Leach S, Lai A, Connors JM, Gascoyne RD, Gallagher RP, Brooks-Wilson AR (2007) Genetic variation in H2AFX contributes to risk of non-Hodgkin lymphoma. Cancer Epidemiol Biomark Prev 16:1098–1106CrossRef

21.

Lu J, Wei Q, Bondy ML, Brewster AM, Bevers TB, Yu TK, Buchholz TA, Meric-Bernstam F, Hunt KK, Singletary SE, Wang LE (2008) Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged < or = 55 years. Breast Cancer Res Treat 110:357–366PubMedCrossRef

22.

Liu Y, Zhang H, Zhou K, Chen L, Xu Z, Zhong Y, Liu H, Li R, Shugart YY, Wei Q, Jin L, Huang F, Lu D, Zhou L (2007) Tagging SNPs in non-homologous end-joining pathway genes and risk of glioma. Carcinogenesis 28:1906–1913PubMedCrossRef

23.

Liu Y, Zhou K, Zhang H, Shugart YY, Chen L, Xu Z, Zhong Y, Liu H, Jin L, Wei Q, Huang F, Lu D, Zhou L (2008) Polymorphisms of LIG4 and XRCC4 involved in the NHEJ pathway interact to modify risk of glioma. Hum Mutat 29:381–389PubMedCrossRef

24.

Zhou K, Liu Y, Zhang H, Liu H, Fan W, Zhong Y, Xu Z, Jin L, Wei Q, Huang F, Lu D, Zhou L (2009) XRCC3 haplotypes and risk of gliomas in a Chinese population: a hospital-based case–control study. Int J Cancer 124:2948–2953PubMedCrossRef

25.

Stephens M, Donnelly P (2003) A comparison of Bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet 73:1162–1169PubMedCrossRef

26.

Choudhury A, Elliott F, Iles MM, Churchman M, Bristow RG, Bishop DT, Kiltie AE (2008) Analysis of variants in DNA damage signalling genes in bladder cancer. BMC Med Genet 9:69PubMedCrossRef

27.

Liu Y, Tseng M, Perdreau SA, Rossi F, Antonescu C, Besmer P, Fletcher JA, Duensing S, Duensing A (2007) Histone H2AX is a mediator of gastrointestinal stromal tumor cell apoptosis following treatment with imatinib mesylate. Cancer Res 67:2685–2692PubMedCrossRef

28.

Srivastava N, Gochhait S, Gupta P, Bamezai RN (2008) Copy number alterations of the H2AFX gene in sporadic breast cancer patients. Cancer Genet Cytogenet 180:121–128PubMedCrossRef

29.

Jane EP, Pollack IF (2010) Enzastaurin induces H2AX phosphorylation to regulate apoptosis via MAPK signalling in malignant glioma cells. Eur J Cancer 46:412–419PubMedCrossRef

30.

IH Consortium (2005) A haplotype map HapMap Project. Nature 437:1299–1320CrossRef

31.

Wrensch M, Bondy ML, Wiencke J, Yost M (1993) Environmental risk factors for primary malignant brain tumors: a review. J Neurooncol 17:47–64PubMedCrossRef

32.

Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B, Simon M, Marie Y, Boisselier B, Delattre JY, Hoang-Xuan K, El Hallani S, Idbaih A, Zelenika D, Andersson U, Henriksson R, Bergenheim AT, Feychting M, Lonn S, Ahlbom A, Schramm J, Linnebank M, Hemminki K, Kumar R, Hepworth SJ, Price A, Armstrong G, Liu Y, Gu X, Yu R, Lau C, Schoemaker M, Muir K, Swerdlow A, Lathrop M, Bondy M, Houlston RS (2009) Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet 41:899–904PubMedCrossRef

33.

Wrensch M, Jenkins RB, Chang JS, Yeh RF, Xiao Y, Decker PA, Ballman KV, Berger M, Buckner JC, Chang S, Giannini C, Halder C, Kollmeyer TM, Kosel ML, LaChance DH, McCoy L, O’Neill BP, Patoka J, Pico AR, Prados M, Quesenberry C, Rice T, Rynearson AL, Smirnov I, Tihan T, Wiemels J, Yang P, Wiencke JK (2009) Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet 41:905–908PubMedCrossRef

Title: Possible association between genetic variants in the H2AFX promoter region and risk of adult glioma in a Chinese Han population
Authors: Weiwei Fan
Keke Zhou
Yingjie Zhao
Wenting Wu
Hongyan Chen
Li Jin
Gong Chen
Jinlong Shi
Qingyi Wei
Tianbao Zhang
Guhong Du
Ying Mao
Daru Lu
Liangfu Zhou
Publication date: 01-11-2011
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2011
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-011-0586-5

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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