Top

Published in:

01-08-2015 | Laboratory Investigation

Genetic variant near TERC influencing the risk of gliomas with older age at diagnosis in a Chinese population

Authors: Dianhong Wang, Enxi Hu, Pei Wu, Wenjing Yuan, Shancai Xu, Zhe Sun, Huaizhang Shi, Jingtao Yuan, Guozhong Li, Shiguang Zhao

Published in: Journal of Neuro-Oncology | Issue 1/2015

Abstract

A recent genome-wide association study has identified an association between rs1920116 near TERC and high-grade glioma in populations of European ancestry. In order to evaluate the effect of the SNP rs1920116 near TERC in the Chinese population, we examined associations of this candidate SNP with glioma in a sample of 1970 Chinese Han individuals. SNP genotype data were available for 980 Chinese glioma patients and 990 healthy controls. Logistic regression analyses were performed to evaluate the association between rs1920116 and glioma risk adjusted for age, gender and stratified by tumor grade where appropriate. The allele G at TERC rs1920116 are risk factors for gliomas, and its association with glioma risk was consistent across tumor subgroups in the Chinese Han population (OR = 1.18–1.21). In order to assess variation in SNP effect size at different patient ages, glioma cases and controls were divided into 3 age strata, in years: <50, 50–59, and 60+. The results of multiple logistic regression analyses indicate that the SNP has age-specific effects on the risk of developing glioma. Our report confirmed the effects of rs1920116 near TERC on glioma occurring in older peoples in the Chinese Han population for the first time. As TERC is a candidate for inter-individual variation in telomere length, our study supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life.

Ahmed R, Oborski MJ, Hwang M, Lieberman FS, Mountz JM (2014) Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods. Cancer Manag Res 6:149–170PubMedCentralPubMed

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 113:1953–1968PubMedCentralPubMedCrossRef

Gu J, Liu Y, Kyritsis AP, Bondy ML (2009) Molecular epidemiology of primary brain tumors. Neurotherapeutics 6:427–435PubMedCrossRef

Liu Y, Shete S, Hosking F, Robertson L, Houlston R, Bondy M (2010) Genetic advances in glioma: susceptibility genes and networks. Curr Opin Genet Dev 20:239–244PubMedCentralPubMedCrossRef

Hemminki K, Tretli S, Sundquist J, Johannesen TB, Granstrom C (2009) Familial risks in nervous-system tumours: a histology-specific analysis from Sweden and Norway. Lancet 10:481–488PubMedCrossRef

Jenkins RB, Xiao Y, Sicotte H, Decker PA, Kollmeyer TM, Hansen HM, Kosel ML, Zheng S, Walsh KM, Rice T, Bracci P, McCoy LS, Smirnov I, Patoka JS, Hsuang G, Wiemels JL, Tihan T, Pico AR, Prados MD, Chang SM, Berger MS, Caron AA, Fink SR, Halder C, Rynearson AL, Fridley BL, Buckner JC, O’Neill BP, Giannini C, Lachance DH, Wiencke JK, Eckel-Passow JE, Wrensch MR (2012) A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation. Nat Genet 44:1122–1125PubMedCentralPubMedCrossRef

Sanson M, Hosking FJ, Shete S, Zelenika D, Dobbins SE, Ma Y, Enciso-Mora V, Idbaih A, Delattre JY, Hoang-Xuan K, Marie Y, Boisselier B, Carpentier C, Wang XW, Di Stefano AL, Labussiere M, Gousias K, Schramm J, Boland A, Lechner D, Gut I, Armstrong G, Liu Y, Yu R, Lau C, Di Bernardo MC, Robertson LB, Muir K, Hepworth S, Swerdlow A, Schoemaker MJ, Wichmann HE, Muller M, Schreiber S, Franke A, Moebus S, Eisele L, Forsti A, Hemminki K, Lathrop M, Bondy M, Houlston RS, Simon M (2011) Chromosome 7p11.2 (EGFR) variation influences glioma risk. Hum Mol Genet 20:2897–2904PubMedCentralPubMedCrossRef

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

Stacey SN, Sulem P, Jonasdottir A, Masson G, Gudmundsson J, Gudbjartsson DF, Magnusson OT, Gudjonsson SA, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Nexo BA, Tjonneland A, Overvad K, Rudnai P, Gurzau E, Koppova K, Hemminki K, Corredera C, Fuentelsaz V, Grasa P, Navarrete S, Fuertes F, Garcia-Prats MD, Sanambrosio E, Panadero A, De Juan A, Garcia A, Rivera F, Planelles D, Soriano V, Requena C, Aben KK, van Rossum MM, Cremers RG, van Oort IM, van Spronsen DJ, Schalken JA, Peters WH, Helfand BT, Donovan JL, Hamdy FC, Badescu D, Codreanu O, Jinga M, Csiki IE, Constantinescu V, Badea P, Mates IN, Dinu DE, Constantin A, Mates D, Kristjansdottir S, Agnarsson BA, Jonsson E, Barkardottir RB, Einarsson GV, Sigurdsson F, Moller PH, Stefansson T, Valdimarsson T, Johannsson OT, Sigurdsson H, Jonsson T, Jonasson JG, Tryggvadottir L, Rice T, Hansen HM, Xiao Y, Lachance DH, O’Neill BP, Kosel ML, Decker PA, Thorleifsson G, Johannsdottir H, Helgadottir HT, Sigurdsson A, Steinthorsdottir V, Lindblom A, Sandler RS, Keku TO, Banasik K, Jorgensen T, Witte DR, Hansen T, Pedersen O, Jinga V, Neal DE, Catalona WJ, Wrensch M, Wiencke J, Jenkins RB, Nagore E, Vogel U, Kiemeney LA, Kumar R, Mayordomo JI, Olafsson JH, Kong A, Thorsteinsdottir U, Rafnar T, Stefansson K (2011) A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. Nat Genet 43:1098–1103PubMedCentralPubMedCrossRef

10.

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 41:905–908PubMedCentralPubMedCrossRef

11.

Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K, Schadendorf D, Kumar R (2013) TERT promoter mutations in familial and sporadic melanoma. Science (New York) 339:959–961CrossRef

12.

Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA (2013) Highly recurrent TERT promoter mutations in human melanoma. Science (New York) 339:957–959CrossRef

13.

Killela PJ, Reitman ZJ, Jiao Y, Bettegowda C, Agrawal N, Diaz LA Jr, Friedman AH, Friedman H, Gallia GL, Giovanella BC, Grollman AP, He TC, He Y, Hruban RH, Jallo GI, Mandahl N, Meeker AK, Mertens F, Netto GJ, Rasheed BA, Riggins GJ, Rosenquist TA, Schiffman M, Shih Ie M, Theodorescu D, Torbenson MS, Velculescu VE, Wang TL, Wentzensen N, Wood LD, Zhang M, McLendon RE, Bigner DD, Kinzler KW, Vogelstein B, Papadopoulos N, Yan H (2013) TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA 110:6021–6026PubMedCentralPubMedCrossRef

14.

Chen H, Chen Y, Zhao Y, Fan W, Zhou K, Liu Y, Zhou L, Mao Y, Wei Q, Xu J, Lu D (2011) Association of sequence variants on chromosomes 20, 11, and 5 (20q13.33, 11q23.3, and 5p15.33) with glioma susceptibility in a Chinese population. Am J Epidemiol 173:915–922PubMedCrossRef

15.

Di Stefano AL, Enciso-Mora V, Marie Y, Desestret V, Labussiere M, Boisselier B, Mokhtari K, Idbaih A, Hoang-Xuan K, Delattre JY, Houlston RS, Sanson M (2013) Association between glioma susceptibility loci and tumour pathology defines specific molecular etiologies. Neuro Oncol 15:542–547PubMedCentralPubMedCrossRef

16.

Li G, Jin T, Liang H, Zhang Z, He S, Tu Y, Yang H, Geng T, Cui G, Chen C, Gao G (2013) RTEL1 tagging SNPs and haplotypes were associated with glioma development. Diagn Pathol 8:83PubMedCentralPubMedCrossRef

17.

Rajaraman P, Melin BS, Wang Z, McKean-Cowdin R, Michaud DS, Wang SS, Bondy M, Houlston R, Jenkins RB, Wrensch M, Yeager M, Ahlbom A, Albanes D, Andersson U, Freeman LE, Buring JE, Butler MA, Braganza M, Carreon T, Feychting M, Fleming SJ, Gapstur SM, Gaziano JM, Giles GG, Hallmans G, Henriksson R, Hoffman-Bolton J, Inskip PD, Johansen C, Kitahara CM, Lathrop M, Liu C, Le Marchand L, Linet MS, Lonn S, Peters U, Purdue MP, Rothman N, Ruder AM, Sanson M, Sesso HD, Severi G, Shu XO, Simon M, Stampfer M, Stevens VL, Visvanathan K, White E, Wolk A, Zeleniuch-Jacquotte A, Zheng W, Decker P, Enciso-Mora V, Fridley B, Gao YT, Kosel M, Lachance DH, Lau C, Rice T, Swerdlow A, Wiemels JL, Wiencke JK, Shete S, Xiang YB, Xiao Y, Hoover RN, Fraumeni JF Jr, Chatterjee N, Hartge P, Chanock SJ (2012) Genome-wide association study of glioma and meta-analysis. Hum Genet 131:1877–1888PubMedCentralPubMedCrossRef

18.

Schoemaker MJ, Robertson L, Wigertz A, Jones ME, Hosking FJ, Feychting M, Lonn S, McKinney PA, Hepworth SJ, Muir KR, Auvinen A, Salminen T, Kiuru A, Johansen C, Houlston RS, Swerdlow AJ (2010) Interaction between 5 genetic variants and allergy in glioma risk. Am J Epidemiol 171:1165–1173PubMedCrossRef

19.

Simon M, Hosking FJ, Marie Y, Gousias K, Boisselier B, Carpentier C, Schramm J, Mokhtari K, Hoang-Xuan K, Idbaih A, Delattre JY, Lathrop M, Robertson LB, Houlston RS, Sanson M (2010) Genetic risk profiles identify different molecular etiologies for glioma. Clin Cancer Res 16:5252–5259PubMedCentralPubMedCrossRef

20.

Wu Y, Tong X, Tang LL, Zhou K, Zhong CH, Jiang S (2014) Associations between the rs6010620 polymorphism in RTEL1 and risk of glioma: a meta-analysis of 20,711 Participants. Asian Pac J Cancer Prev 15:7163–7167PubMedCrossRef

21.

Houlston RS, Cheadle J, Dobbins SE, Tenesa A, Jones AM, Howarth K, Spain SL, Broderick P, Domingo E, Farrington S, Prendergast JG, Pittman AM, Theodoratou E, Smith CG, Olver B, Walther A, Barnetson RA, Churchman M, Jaeger EE, Penegar S, Barclay E, Martin L, Gorman M, Mager R, Johnstone E, Midgley R, Niittymaki I, Tuupanen S, Colley J, Idziaszczyk S, Thomas HJ, Lucassen AM, Evans DG, Maher ER, Maughan T, Dimas A, Dermitzakis E, Cazier JB, Aaltonen LA, Pharoah P, Kerr DJ, Carvajal-Carmona LG, Campbell H, Dunlop MG, Tomlinson IP (2010) Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33. Nat Genet 42:973–977PubMedCrossRef

22.

Maubaret CG, Salpea KD, Romanoski CE, Folkersen L, Cooper JA, Stephanou C, Li KW, Palmen J, Hamsten A, Neil A, Stephens JW, Lusis AJ, Eriksson P, Talmud PJ, Humphries SE (2013) Association of TERC and OBFC1 haplotypes with mean leukocyte telomere length and risk for coronary heart disease. PLoS ONE 8:e83122PubMedCentralPubMedCrossRef

23.

Walsh KM, Codd V, Smirnov IV, Rice T, Decker PA, Hansen HM, Kollmeyer T, Kosel ML, Molinaro AM, McCoy LS, Bracci PM, Cabriga BS, Pekmezci M, Zheng S, Wiemels JL, Pico AR, Tihan T, Berger MS, Chang SM, Prados MD, Lachance DH, O’Neill BP, Sicotte H, Eckel-Passow JE, van der Harst P, Wiencke JK, Samani NJ, Jenkins RB, Wrensch MR (2014) Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. Nat Genet 46:731–735PubMedCentralPubMedCrossRef

24.

Blackburn EH, Greider CW, Szostak JW (2006) Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging. Nat Med 12:1133–1138PubMedCrossRef

25.

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109PubMedCentralPubMedCrossRef

26.

Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK (2002) The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61: 215–225 (discussion 226–219)

27.

Hackett JA, Greider CW (2002) Balancing instability: dual roles for telomerase and telomere dysfunction in tumorigenesis. Oncogene 21:619–626PubMedCrossRef

28.

Codd V, Nelson CP, Albrecht E, Mangino M, Deelen J, Buxton JL, Hottenga JJ, Fischer K, Esko T, Surakka I, Broer L, Nyholt DR, Mateo Leach I, Salo P, Hagg S, Matthews MK, Palmen J, Norata GD, O’Reilly PF, Saleheen D, Amin N, Balmforth AJ, Beekman M, de Boer RA, Bohringer S, Braund PS, Burton PR, de Craen AJ, Denniff M, Dong Y, Douroudis K, Dubinina E, Eriksson JG, Garlaschelli K, Guo D, Hartikainen AL, Henders AK, Houwing-Duistermaat JJ, Kananen L, Karssen LC, Kettunen J, Klopp N, Lagou V, van Leeuwen EM, Madden PA, Magi R, Magnusson PK, Mannisto S, McCarthy MI, Medland SE, Mihailov E, Montgomery GW, Oostra BA, Palotie A, Peters A, Pollard H, Pouta A, Prokopenko I, Ripatti S, Salomaa V, Suchiman HE, Valdes AM, Verweij N, Vinuela A, Wang X, Wichmann HE, Widen E, Willemsen G, Wright MJ, Xia K, Xiao X, van Veldhuisen DJ, Catapano AL, Tobin MD, Hall AS, Blakemore AI, van Gilst WH, Zhu H, Consortium C, Erdmann J, Reilly MP, Kathiresan S, Schunkert H, Talmud PJ, Pedersen NL, Perola M, Ouwehand W, Kaprio J, Martin NG, van Duijn CM, Hovatta I, Gieger C, Metspalu A, Boomsma DI, Jarvelin MR, Slagboom PE, Thompson JR, Spector TD, van der Harst P, Samani NJ (2013) Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet 45:422–427PubMedCentralPubMedCrossRef

29.

Jones AM, Beggs AD, Carvajal-Carmona L, Farrington S, Tenesa A, Walker M, Howarth K, Ballereau S, Hodgson SV, Zauber A, Bertagnolli M, Midgley R, Campbell H, Kerr D, Dunlop MG, Tomlinson IP (2012) TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres. Gut 61:248–254PubMedCentralPubMedCrossRef

30.

Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, Loyd JE, Cosgrove GP, Lynch D, Groshong S, Collard HR, Wolters PJ, Bradford WZ, Kossen K, Seiwert SD, du Bois RM, Garcia CK, Devine MS, Gudmundsson G, Isaksson HJ, Kaminski N, Zhang Y, Gibson KF, Lancaster LH, Cogan JD, Mason WR, Maher TM, Molyneaux PL, Wells AU, Moffatt MF, Selman M, Pardo A, Kim DS, Crapo JD, Make BJ, Regan EA, Walek DS, Daniel JJ, Kamatani Y, Zelenika D, Smith K, McKean D, Pedersen BS, Talbert J, Kidd RN, Markin CR, Beckman KB, Lathrop M, Schwarz MI, Schwartz DA (2013) Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet 45:613–620PubMedCentralPubMedCrossRef

Title: Genetic variant near TERC influencing the risk of gliomas with older age at diagnosis in a Chinese population
Authors: Dianhong Wang
Enxi Hu
Pei Wu
Wenjing Yuan
Shancai Xu
Zhe Sun
Huaizhang Shi
Jingtao Yuan
Guozhong Li
Shiguang Zhao
Publication date: 01-08-2015
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2015
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-015-1819-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Genetic variant near TERC influencing the risk of gliomas with older age at diagnosis in a Chinese population

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2015

Venous thromboembolism (VTE) and glioblastoma

Prognostic implication of progression pattern after anti-VEGF bevacizumab treatment for recurrent malignant gliomas

Incidence, risk factors, and reasons for hospitalization among glioblastoma patients receiving chemoradiation

Erratum to: Disseminated oligodendroglial-like leptomeningeal tumors: preliminary diagnostic and therapeutic results for a novel tumor entity

Combined treatment by octreotide and everolimus: Octreotide enhances inhibitory effect of everolimus in aggressive meningiomas

Can lateral ventricle contact predict the ontogeny and prognosis of glioblastoma?