Skip to main content

Advertisement

SpringerLink
Log in

TERT Gene rs2736100 and rs2736098 Polymorphisms are Associated with Increased Cancer Risk: A Meta-Analysis

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Abnormal telomerase activity plays a key role in the development of carcinogenesis. The variants rs2736100 and rs2736098 of the telomerase reverse transcriptase (TERT) gene, which encodes the telomerase catalytic subunit, are associated with the risk of different types of cancers. However, the results remain controversy. We conducted a meta-analysis to more precisely assess this association. We comprehensively searched the PubMed and Web of Science databases up to June 1, 2020, and retrieved a total of 103 studies in 82 articles, including 89,320 cases and 121,654 controls. Among these studies, 69 published studies including 75,274 cases and 10,3248 controls were focused on rs2736100, and 34 published studies including 14,046 cases and 18,362 controls were focused on rs2736098. The results showed a strong association between variant rs2736100 and cancer risk in all populations. (G vs. T: OR 1.18, 95% CI 1.12–1.24; TG+GG vs. TT: OR 1.23, 95% CI 1.15–1.31; GG vs. TG+TT: OR 1.25, 95% CI 1.16–1.36); the variant rs2736098 was associated with cancer risk in all populations as well (A vs. G: OR 1.13, 95% CI 1.05–1.22; GA+AA vs. GG: OR 1.15, 95% CI 1.04–1.27; AA vs. GA+GG: OR 1.22, 95% CI 1.10–1.38). Stratified analysis based on the cancer type indicated that rs2736100 was associated with an increased risk of thyroid cancer, bladder cancer, lung cancer, glioma, and myeloproliferative neoplasms. rs2736098 only increased the risk of bladder cancer and lung cancer. Moreover, the TERT variants rs2736100 and rs2736098 were associated with a decreased risk of breast cancer and colorectal cancer. The variants rs2736098 and rs2736100 located in 5p15.33 around TERT were associated with increased cancer risk in all populations. These two variants had bidirectional effects in different tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

BC:

Breast cancer

BCC:

Basal cell carcinoma

CC:

Cervical cancer

CML:

Chronic myeloid leukemia

CLL:

Chronic lymphocytic leukemia

CRC:

Colorectal cancer

DLBCL:

Diffuse large B-cell lymphoma

ESCC:

Esophageal squamous cell carcinoma

GBC:

Gallbladder cancer

GC:

Gastric cancer

HCC:

Hepatocellular carcinoma

HNSC:

Squamous cell carcinoma of the head and neck

LC:

Lung cancer

LSCC:

Laryngeal squamous cell carcinoma

MAF:

Minor allele frequency

MPN:

Myeloproliferative neoplasms

NC:

Nasopharyngeal carcinoma

OSCC:

Oral squamous cell carcinoma

PDAC:

Pancreatic ductal adenocarcinoma

PEN:

Pancreatic adenocarcinoma

PLC:

Pharynx–larynx cancer

PTC:

Papillary thyroid carcinoma

RC:

Rectal cancer

RCC:

Renal cell carcinoma

SCC:

Squamous cell carcinoma

UTUC:

Upper tract urothelial carcinomas

References

  • Adel Fahmideh M, Lavebratt C, Schüz J, Röösli M, Tynes T, Grotzer MA, Johansen C, Kuehni CE, Lannering B, Prochazka M, Schmidt LS, Feychting M (2015) CCDC26, CDKN2BAS, RTEL1 and TERT polymorphisms in pediatric brain tumor susceptibility. Carcinogenesis 36(8):876–882. https://doi.org/10.1093/carcin/bgv074

    Article  CAS  PubMed  Google Scholar 

  • Aydin M, Sümbül AT, Camuz Hilaloğullari G, Bayram S (2018) Genetic polymorphisms in human telomerase reverse transcriptase (hTERT) gene polymorphisms do not associated with breast cancer in patients in a Turkish population: hospital-based case–control study. Cell Mol Biol 64(3):108–115. https://doi.org/10.14715/cmb/2018.64.1.3

    Article  PubMed  Google Scholar 

  • Bae EY, Lee SY, Kang BK, Lee EJ, Choi YY, Kang HG, Choi JE, Jeon HS, Lee WK, Kam S, Shin KM, Jin G, Yoo SS, Lee J, Cha SI, Kim CH, Jung TH, Park JY (2012) Replication of results of genome-wide association studies on lung cancer susceptibility loci in a Korean population. Respirology 17(4):699–706. https://doi.org/10.1111/j.1440-1843.2012.02165.x

    Article  PubMed  Google Scholar 

  • Bayram S, Ülger Y, Sümbül AT, Kaya BY, Genç A, Rencüzoğullari E, Dadaş E (2016) Polymorphisms in human telomerase reverse transcriptase (hTERT) gene and susceptibility to gastric cancer in a Turkish population: hospital-based case–control study. Gene 585(1):84–92. https://doi.org/10.1016/j.gene.2016.03.030

    Article  CAS  PubMed  Google Scholar 

  • Bell RJ, Rube HT, Xavier-Magalhães A, Costa BM, Mancini A, Song JS, Costello JF (2016) Understanding TERT promoter mutations: a common path to immortality. Mol Cancer Res 14(4):315–323. https://doi.org/10.1158/1541-7786.Mcr-16-0003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boukamp P, Popp S, Krunic D (2005) Telomere-dependent chromosomal instability. J Investig Dermatol Symp Proc 10(2):89–94. https://doi.org/10.1111/j.1087-0024.2005.200401.x

    Article  CAS  PubMed  Google Scholar 

  • Campa D, Rizzato C, Stolzenberg-Solomon R, Pacetti P, Vodicka P, Cleary SP, Capurso G, Bueno-de-Mesquita HB, Werner J, Gazouli M, Butterbach K, Ivanauskas A, Giese N, Petersen GM, Fogar P, Wang Z, Bassi C, Ryska M, Theodoropoulos GE, Kooperberg C, Li D, Greenhalf W, Pasquali C, Hackert T, Fuchs CS, Mohelnikova-Duchonova B, Sperti C, Funel N, Dieffenbach AK, Wareham NJ, Buring J, Holcátová I, Costello E, Zambon CF, Kupcinskas J, Risch HA, Kraft P, Bracci PM, Pezzilli R, Olson SH, Sesso HD, Hartge P, Strobel O, Małecka-Panas E, Visvanathan K, Arslan AA, Pedrazzoli S, Souček P, Gioffreda D, Key TJ, Talar-Wojnarowska R, Scarpa A, Mambrini A, Jacobs EJ, Jamroziak K, Klein A, Tavano F, Bambi F, Landi S, Austin MA, Vodickova L, Brenner H, Chanock SJ, Delle Fave G, Piepoli A, Cantore M, Zheng W, Wolpin BM, Amundadottir LT, Canzian F (2015) TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. Int J Cancer 137(9):2175–2183. https://doi.org/10.1002/ijc.29590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campa D, Matarazzi M, Greenhalf W, Bijlsma M, Saum KU, Pasquali C, van Laarhoven H, Szentesi A, Federici F, Vodicka P, Funel N, Pezzilli R, Bueno-de-Mesquita HB, Vodickova L, Basso D, Obazee O, Hackert T, Soucek P, Cuk K, Kaiser J, Sperti C, Lovecek M, Capurso G, Mohelnikova-Duchonova B, Khaw KT, König AK, Kupcinskas J, Kaaks R, Bambi F, Archibugi L, Mambrini A, Cavestro GM, Landi S, Hegyi P, Izbicki JR, Gioffreda D, Zambon CF, Tavano F, Talar-Wojnarowska R, Jamroziak K, Key TJ, Fave GD, Strobel O, Jonaitis L, Andriulli A, Lawlor RT, Pirozzi F, Katzke V, Valsuani C, Vashist YK, Brenner H, Canzian F (2019) Genetic determinants of telomere length and risk of pancreatic cancer: a PANDoRA study. Int J Cancer 144(6):1275–1283. https://doi.org/10.1002/ijc.31928

    Article  CAS  PubMed  Google Scholar 

  • Carkic J, Nikolic N, Radojevic-Skodric S, Kuzmanovic-Pficer J, Brajovic G, Antunovic M, Milasin J, Popovic B (2016) The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma. J Oral Sci 58(4):449–458. https://doi.org/10.2334/josnusd.16-0108

    Article  CAS  PubMed  Google Scholar 

  • 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(8):915–922. https://doi.org/10.1093/aje/kwq457

    Article  PubMed  Google Scholar 

  • Chen XF, Cai S, Chen QG, Ni ZH, Tang JH, Xu DW, Wang XB (2012) Multiple variants of TERT and CLPTM1L constitute risk factors for lung adenocarcinoma. Genet Mol Res 11(1):370–378. https://doi.org/10.4238/2012.February.16.2

    Article  CAS  PubMed  Google Scholar 

  • Choi BJ, Yoon JH, Kim O, Choi WS, Nam SW, Lee JY, Park WS (2015) Influence of the hTERT rs2736100 polymorphism on telomere length in gastric cancer. World J Gastroenterol 21(31):9328–9336. https://doi.org/10.3748/wjg.v21.i31.9328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dahlström J, Liu T, Yuan X, Saft L, Ghaderi M, Wei YB, Lavebratt C, Li P, Zheng C, Björkholm M, Xu D (2016) TERT rs2736100 genotypes are associated with differential risk of myeloproliferative neoplasms in Swedish and Chinese male patient populations. Ann Hematol 95(11):1825–1832. https://doi.org/10.1007/s00277-016-2787-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Martino M, Taus C, Lucca I, Hofbauer SL, Haitel A, Shariat SF, Klatte T (2016) Association of human telomerase reverse transcriptase gene polymorphisms, serum levels, and telomere length with renal cell carcinoma risk and pathology. Mol Carcinog 55(10):1458–1466. https://doi.org/10.1002/mc.22388

    Article  CAS  PubMed  Google Scholar 

  • Ding CY, Hu LM, Hu ZB, Shen HB (2011) The relationship between gene polymorphism of telomerase reverse transcriptase and susceptibility to hepatocellular carcinoma. Zhonghua yu fang yi xue za zhi. Chin J Prev Med 45(7):593–596

    CAS  Google Scholar 

  • Du J, Zhu X, Xie C, Dai N, Gu Y, Zhu M, Wang C, Gao Y, Pan F, Ren C, Ji Y, Dai J, Ma H, Jiang Y, Chen J, Yi H, Zhao Y, Hu Z, Shen H, Jin G (2015) Telomere length, genetic variants and gastric cancer risk in a Chinese population. Carcinogenesis 36(9):963–970. https://doi.org/10.1093/carcin/bgv075

    Article  CAS  PubMed  Google Scholar 

  • Essa ES, Alagizy HA (2018) Association of MNS16A VNTR and hTERT rs2736098: G>A polymorphisms with susceptibility to diffuse large B-cell lymphoma. Tumori J 104(3):165–171. https://doi.org/10.5301/tj.5000653

    Article  CAS  Google Scholar 

  • Gago-Dominguez M, Jiang X, Conti DV, Castelao JE, Stern MC, Cortessis VK, Pike MC, Xiang YB, Gao YT, Yuan JM, Van Den Berg DJ (2011) Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk: findings from the Los Angeles-Shanghai bladder case–control study. Carcinogenesis 32(2):197–202. https://doi.org/10.1093/carcin/bgq233

    Article  CAS  PubMed  Google Scholar 

  • Gao L, Thakur A, Liang Y, Zhang S, Wang T, Chen T, Meng J, Wang L, Wu F, Jin T, Li X, Liu JJ, Chen C, Chen M (2014) Polymorphisms in the TERT gene are associated with lung cancer risk in the Chinese Han population. Eur J Cancer Prev 23(6):497–501. https://doi.org/10.1097/cej.0000000000000086

    Article  CAS  PubMed  Google Scholar 

  • Gaspar TB, Sa A, Lopes JM, Sobrinho-Simoes M, Soares P, Vinagre J (2018) Telomere maintenance mechanisms in cancer. Genes. https://doi.org/10.3390/genes9050241

    Article  PubMed  Google Scholar 

  • Ge M, Shi M, An C, Yang W, Nie X, Zhang J, Lv Z, Li J, Zhou L, Du Z, Yang M (2016) Functional evaluation of TERT-CLPTM1L genetic variants associated with susceptibility of papillary thyroid carcinoma. Sci Rep 6:26037. https://doi.org/10.1038/srep26037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gong L, Xu Y, Hu YQ, Ding QJ, Yi CH, Huang W, Zhou M (2016) hTERT gene polymorphism correlates with the risk and the prognosis of thyroid cancer. Cancer Biomark 17(2):195–204. https://doi.org/10.3233/cbm-160631

    Article  CAS  PubMed  Google Scholar 

  • Hashemi M, Amininia S, Ebrahimi M, Hashemi SM, Taheri M, Ghavami S (2014) Association between hTERT polymorphisms and the risk of breast cancer in a sample of Southeast Iranian population. BMC Res Notes 7:895. https://doi.org/10.1186/1756-0500-7-895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hofer P, Baierl A, Bernhart K, Leeb G, Mach K, Micksche M, Gsur A (2012) Association of genetic variants of human telomerase with colorectal polyps and colorectal cancer risk. Mol Carcinog 51(Suppl 1):E176-182. https://doi.org/10.1002/mc.21911

    Article  CAS  PubMed  Google Scholar 

  • Hosgood HD 3rd, Song M, Hsiung CA, Yin Z, Shu XO, Wang Z, Chatterjee N, Zheng W, Caporaso N, Burdette L, Yeager M, Berndt SI, Landi MT, Chen CJ, Chang GC, Hsiao CF, Tsai YH, Chien LH, Chen KY, Huang MS, Su WC, Chen YM, Chen CH, Yang TY, Wang CL, Hung JY, Lin CC, Perng RP, Chen CY, Chen KC, Li YJ, Yu CJ, Chen YS, Chen YH, Tsai FY, Kim C, Seow WJ, Bassig BA, Wu W, Guan P, He Q, Gao YT, Cai Q, Chow WH, Xiang YB, Lin D, Wu C, Wu YL, Shin MH, Hong YC, Matsuo K, Chen K, Wong MP, Lu D, Jin L, Wang JC, Seow A, Wu T, Shen H, Fraumeni JF Jr, Yang PC, Chang IS, Zhou B, Chanock SJ, Rothman N, Lan Q (2015) Interactions between household air pollution and GWAS-identified lung cancer susceptibility markers in the Female lung cancer consortium in Asia (FLCCA). Hum Genet 134(3):333–341. https://doi.org/10.1007/s00439-014-1528-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu Z, Wu C, Shi Y, Guo H, Zhao X, Yin Z, Yang L, Dai J, Hu L, Tan W, Li Z, Deng Q, Wang J, Wu W, Jin G, Jiang Y, Yu D, Zhou G, Chen H, Guan P, Chen Y, Shu Y, Xu L, Liu X, Liu L, Xu P, Han B, Bai C, Zhao Y, Zhang H, Yan Y, Ma H, Chen J, Chu M, Lu F, Zhang Z, Chen F, Wang X, Jin L, Lu J, Zhou B, Lu D, Wu T, Lin D, Shen H (2011) A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese. Nat Genet 43(8):792–796. https://doi.org/10.1038/ng.875

    Article  CAS  PubMed  Google Scholar 

  • Ito H, McKay JD, Hosono S, Hida T, Yatabe Y, Mitsudomi T, Brennan P, Tanaka H, Matsuo K (2012) Association between a genome-wide association study-identified locus and the risk of lung cancer in Japanese population. J Thorac Oncol 7(5):790–798. https://doi.org/10.1097/JTO.0b013e3182475028

    Article  CAS  PubMed  Google Scholar 

  • Jäger R, Harutyunyan AS, Rumi E, Pietra D, Berg T, Olcaydu D, Houlston RS, Cazzola M, Kralovics R (2014) Common germline variation at the TERT locus contributes to familial clustering of myeloproliferative neoplasms. Am J Hematol 89(12):1107–1110. https://doi.org/10.1002/ajh.23842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jannuzzi AT, Karaman E, Oztas E, Yanar HT, Özhan G (2015) Telomerase reverse transcriptase (TERT) gene variations and susceptibility of colorectal cancer. Genet Test Mol Biomark 19(12):692–697. https://doi.org/10.1089/gtmb.2015.0150

    Article  CAS  Google Scholar 

  • Jaworowska E, Trubicka J, Lener MR, Masojć B, Złowocka-Perłowska E, McKay JD, Renard H, Oszutowska D, Wokołorczyk D, Lubiński J, Grodzki T, Serwatowski P, Nej-Wołosiak K, Tołoczko-Grabarek A, Sikorski A, Słojewski M, Jakubowska A, Cybulski C, Lubiński J, Scott RJ (2011) Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33 in the Polish population. PLoS ONE 6(9):e25057. https://doi.org/10.1371/journal.pone.0025057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kinnersley B, Migliorini G, Broderick P, Whiffin N, Dobbins SE, Casey G, Hopper J, Sieber O, Lipton L, Kerr DJ, Dunlop MG, Tomlinson IP, Houlston RS (2012) The TERT variant rs2736100 is associated with colorectal cancer risk. Br J Cancer 107(6):1001–1008. https://doi.org/10.1038/bjc.2012.329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohno T, Kunitoh H, Mimaki S, Shiraishi K, Kuchiba A, Yamamoto S, Yokota J (2011) Contribution of the TP53, OGG1, CHRNA3, and HLA-DQA1 genes to the risk for lung squamous cell carcinoma. J Thorac Oncol 6(4):813–817. https://doi.org/10.1097/JTO.0b013e3181ee80ef

    Article  PubMed  Google Scholar 

  • Krahling T, Balassa K, Kiss KP, Bors A, Batai A, Halm G, Egyed M, Fekete S, Remenyi P, Masszi T, Tordai A, Andrikovics H (2016) Co-occurrence of myeloproliferative neoplasms and solid tumors is attributed to a synergism between cytoreductive therapy and the common TERT polymorphism rs2736100. Cancer Epidemiol Biomark Prev 25(1):98–104. https://doi.org/10.1158/1055-9965.Epi-15-0805

    Article  Google Scholar 

  • Lan Q, Cawthon R, Gao Y, Hu W, Hosgood HD 3rd, Barone-Adesi F, Ji BT, Bassig B, Chow WH, Shu X, Cai Q, Xiang Y, Berndt S, Kim C, Chanock S, Zheng W, Rothman N (2013) Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China. PLoS ONE 8(3):e59230. https://doi.org/10.1371/journal.pone.0059230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li C, Yin Z, Wu W, Li X, Ren Y, Zhou B (2013) Genetic variations in TERT-CLPTM1L genes and risk of lung cancer in Chinese women nonsmokers rs2736098 and CLPTM1L-rs4016981. PLoS ONE 8(5):e64988. https://doi.org/10.1371/journal.pone.0064988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li T, Xian Y, Tian T, Zhuang X, Chu M (2016a) New evidence of TERT rs2736098 polymorphism and cancer risk: an updated meta-analysis. J BUON 21(2):491–497

    PubMed  Google Scholar 

  • Li X, Xu X, Fang J, Wang L, Mu Y, Zhang P, Yao Z, Ma Z, Liu Z (2016b) Rs2853677 modulates Snail1 binding to the TERT enhancer and affects lung adenocarcinoma susceptibility. Oncotarget 7(25):37825–37838. https://doi.org/10.18632/oncotarget.9339

    Article  PubMed  PubMed Central  Google Scholar 

  • Li H, Xu Y, Mei H, Peng L, Li X, Tang J (2017) The TERT rs2736100 polymorphism increases cancer risk: a meta-analysis. Oncotarget 8(24):38693–38705. https://doi.org/10.18632/oncotarget.16309

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Shi F (2020) Associations of telomerase reverse transcriptase rs10069690 and rs2736100 polymorphisms with papillary thyroid carcinoma. Eur J Cancer Prev 29(3):259–265. https://doi.org/10.1097/cej.0000000000000536

    Article  CAS  PubMed  Google Scholar 

  • Liu SG, Ma L, Cen QH, Huang JS, Zhang JX, Zhang JJ (2015) Association of genetic polymorphisms in TERT-CLPTM1L with lung cancer in a Chinese population. Genet Mol Res 14(2):4469–4476. https://doi.org/10.4238/2015.May.4.4

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Goldstein AM, Hsu WL, Yu KJ, Chien YC, Ko JY, Jian JJ, Tsou YA, Leu YS, Liao LJ, Chang YL, Wang CP, Wu JS, Hua CH, Lee JC, Yang TL, Hsiao CK, Wu MS, Tsai MH, Huang KK, Yu K, Jones K, Zhu B, Yeager M, Yu G, Lou PJ, Chen CJ, Hildesheim A (2019) Evaluation of rare and common variants from suspected familial or sporadic nasopharyngeal carcinoma (NPC) susceptibility genes in sporadic NPC. Cancer Epidemiol Biomark Prev 28(10):1682–1686. https://doi.org/10.1158/1055-9965.EPI-19-0007

    Article  CAS  Google Scholar 

  • Llorca-Cardeñosa MJ, Peña-Chilet M, Mayor M, Gomez-Fernandez C, Casado B, Martin-Gonzalez M, Carretero G, Lluch A, Martinez-Cadenas C, Ibarrola-Villava M, Ribas G (2014) Long telomere length and a TERT-CLPTM1 locus polymorphism association with melanoma risk. Eur J Cancer 50(18):3168–3177. https://doi.org/10.1016/j.ejca.2014.09.017

    Article  CAS  PubMed  Google Scholar 

  • Ma Z, Hu Q, Chen Z, Tao S, Macnamara L, Kim ST, Tian L, Xu K, Ding Q, Zheng SL, Sun J, Xia G, Xu J (2013) Systematic evaluation of bladder cancer risk-associated single-nucleotide polymorphisms in a Chinese population. Mol Carcinog 52(11):916–921. https://doi.org/10.1002/mc.21932

    Article  CAS  PubMed  Google Scholar 

  • Matsuguma M, Yujiri T, Yamamoto K, Kajimura Y, Tokunaga Y, Tanaka M, Tanaka Y, Nakamura Y, Tanizawa Y (2019) TERT and JAK2 polymorphisms define genetic predisposition to myeloproliferative neoplasms in Japanese patients. Int J Hematol 110(6):690–698. https://doi.org/10.1007/s12185-019-02742-7

    Article  CAS  PubMed  Google Scholar 

  • Mocellin S, Verdi D, Pooley KA, Landi MT, Egan KM, Baird DM, Prescott J, De Vivo I, Nitti D (2012) Telomerase reverse transcriptase locus polymorphisms and cancer risk: a field synopsis and meta-analysis. J Natl Cancer Inst 104(11):840–854. https://doi.org/10.1093/jnci/djs222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mosrati MA, Willander K, Falk IJ, Hermanson M, Höglund M, Stockelberg D, Wei Y, Lotfi K, Söderkvist P (2015) Association between TERT promoter polymorphisms and acute myeloid leukemia risk and prognosis. Oncotarget 6(28):25109–25120. https://doi.org/10.18632/oncotarget.4668

    Article  PubMed  PubMed Central  Google Scholar 

  • Myneni AA, Chang SC, Niu R, Liu L, Ochs-Balcom HM, Li Y, Zhang C, Zhao B, Shi J, Han X, Li J, Su J, Cai L, Yu S, Zhang ZF, Mu L (2013) Genetic polymorphisms of TERT and CLPTM1L and risk of lung cancer–a case-control study in a Chinese population. Lung Cancer 80(2):131–137. https://doi.org/10.1016/j.lungcan.2013.01.021

    Article  PubMed  Google Scholar 

  • Nan H, Qureshi AA, Prescott J, De Vivo I, Han J (2011) Genetic variants in telomere-maintaining genes and skin cancer risk. Hum Genet 129(3):247–253. https://doi.org/10.1007/s00439-010-0921-5

    Article  PubMed  Google Scholar 

  • Obazee O, Capurso G, Tavano F, Archibugi L, De Bonis A, Greenhalf W, Key T, Pasquali C, Milanetto AC, Hackert T, Fogar P, Liço V, Dervenis C, Lawlor RT, Landoni L, Gazouli M, Zambon CF, Funel N, Strobel O, Jamroziak K, Cantù C, Malecka-Panas E, Landi S, Neoptolemos JP, Basso D, Talar-Wojnarowska R, Rinzivillo M, Andriulli A, Canzian F, Campa D (2018) Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms. Carcinogenesis 39(3):360–367. https://doi.org/10.1093/carcin/bgx150

    Article  CAS  PubMed  Google Scholar 

  • Oztas E, Kara H, Kara ZP, Aydogan MU, Uras C, Ozhan G (2016) Association between human telomerase reverse transcriptase gene variations and risk of developing breast cancer. Genet Test Mol Biomark 20(8):459–464. https://doi.org/10.1089/gtmb.2015.0339

    Article  CAS  Google Scholar 

  • Pellatt AJ, Wolff RK, Herrick J, Lundgreen A, Slattery ML (2013a) TERT’s role in colorectal carcinogenesis. Mol Carcinog 52(7):507–513. https://doi.org/10.1002/mc.21885

    Article  CAS  PubMed  Google Scholar 

  • Pellatt AJ, Wolff RK, Torres-Mejia G, John EM, Herrick JS, Lundgreen A, Baumgartner KB, Giuliano AR, Hines LM, Fejerman L, Cawthon R, Slattery ML (2013b) Telomere length, telomere-related genes, and breast cancer risk: the breast cancer health disparities study. Genes Chromosom Cancer 52(7):595–609. https://doi.org/10.1002/gcc.22056

    Article  CAS  PubMed  Google Scholar 

  • Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, Sigurdsson A, Jakobsdottir M, Helgadottir H, Thorlacius S, Aben KK, Blöndal T, Thorgeirsson TE, Thorleifsson G, Kristjansson K, Thorisdottir K, Ragnarsson R, Sigurgeirsson B, Skuladottir H, Gudbjartsson T, Isaksson HJ, Einarsson GV, Benediktsdottir KR, Agnarsson BA, Olafsson K, Salvarsdottir A, Bjarnason H, Asgeirsdottir M, Kristinsson KT, Matthiasdottir S, Sveinsdottir SG, Polidoro S, Höiom V, Botella-Estrada R, Hemminki K, Rudnai P, Bishop DT, Campagna M, Kellen E, Zeegers MP, de Verdier P, Ferrer A, Isla D, Vidal MJ, Andres R, Saez B, Juberias P, Banzo J, Navarrete S, Tres A, Kan D, Lindblom A, Gurzau E, Koppova K, de Vegt F, Schalken JA, van der Heijden HF, Smit HJ, Termeer RA, Oosterwijk E, van Hooij O, Nagore E, Porru S, Steineck G, Hansson J, Buntinx F, Catalona WJ, Matullo G, Vineis P, Kiltie AE, Mayordomo JI, Kumar R, Kiemeney LA, Frigge ML, Jonsson T, Saemundsson H, Barkardottir RB, Jonsson E, Jonsson S, Olafsson JH, Gulcher JR, Masson G, Gudbjartsson DF, Kong A, Thorsteinsdottir U, Stefansson K (2009) Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 41(2):221–227. https://doi.org/10.1038/ng.296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(12):1877–1888. https://doi.org/10.1007/s00439-012-1212-0

    Article  PubMed  PubMed Central  Google Scholar 

  • Shadrina AS, Boyarskikh UA, Oskina NA, Sinkina TV, Lazarev AF, Petrova VD, Filipenko ML (2015) TERT polymorphisms rs2853669 and rs7726159 influence on prostate cancer risk in Russian population. Tumour Biol 36(2):841–847. https://doi.org/10.1007/s13277-014-2688-0

    Article  CAS  PubMed  Google Scholar 

  • Shen CT, Zhang GQ, Qiu ZL, Song HJ, Sun ZK, Luo QY (2019) Targeted next-generation sequencing in papillary thyroid carcinoma patients looking for germline variants predisposing to the disease. Endocrine 64(3):622–631. https://doi.org/10.1007/s12020-019-01878-0

    Article  CAS  PubMed  Google Scholar 

  • Sheng X, Tong N, Tao G, Luo D, Wang M, Fang Y, Li J, Xu M, Zhang Z, Wu D (2013) TERT polymorphisms modify the risk of acute lymphoblastic leukemia in Chinese children. Carcinogenesis 34(1):228–235. https://doi.org/10.1093/carcin/bgs325

    Article  CAS  PubMed  Google Scholar 

  • Shiraishi K, Kunitoh H, Daigo Y, Takahashi A, Goto K, Sakamoto H, Ohnami S, Shimada Y, Ashikawa K, Saito A, Watanabe S, Tsuta K, Kamatani N, Yoshida T, Nakamura Y, Yokota J, Kubo M, Kohno T (2012) A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nat Genet 44(8):900–903. https://doi.org/10.1038/ng.2353

    Article  CAS  PubMed  Google Scholar 

  • Shiraishi K, Okada Y, Takahashi A, Kamatani Y, Momozawa Y, Ashikawa K, Kunitoh H, Matsumoto S, Takano A, Shimizu K, Goto A, Tsuta K, Watanabe SI, Ohe Y, Watanabe Y, Goto Y, Nokihara H, Furuta K, Yoshida A, Goto K, Hishida T, Tsuboi M, Tsuchihara K, Miyagi Y, Nakayama H, Yokose T, Tanaka K, Nagashima T, Ohtaki Y, Maeda D, Imai K, Minamiya Y, Sakamoto H, Saito A, Shimada Y, Sunami K, Saito M, Inazawa J, Nakamura Y, Yoshida T, Yokota J, Matsuda F, Matsuo K, Daigo Y, Kubo M, Kohno T (2016) Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma. Nat Commun 7:12451. https://doi.org/10.1038/ncomms12451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh V, Jaiswal PK, Mittal RD (2014) Replicative study of GWAS TP63C/T, TERTC/T, and SLC14A1C/T with susceptibility to bladder cancer in North Indians. Urol Oncol 32(8):1209–1214. https://doi.org/10.1016/j.urolonc.2014.05.013

    Article  CAS  PubMed  Google Scholar 

  • Snetselaar R, van Oosterhout MFM, Grutters JC, van Moorsel CHM (2018) Telomerase reverse transcriptase polymorphism rs2736100: a balancing act between cancer and non-cancer disease, a meta-analysis. Front Med 5:41. https://doi.org/10.3389/fmed.2018.00041

    Article  Google Scholar 

  • Speedy HE, Di Bernardo MC, Sava GP, Dyer MJ, Holroyd A, Wang Y, Sunter NJ, Mansouri L, Juliusson G, Smedby KE, Roos G, Jayne S, Majid A, Dearden C, Hall AG, Mainou-Fowler T, Jackson GH, Summerfield G, Harris RJ, Pettitt AR, Allsup DJ, Bailey JR, Pratt G, Pepper C, Fegan C, Rosenquist R, Catovsky D, Allan JM, Houlston RS (2014) A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia. Nat Genet 46(1):56–60. https://doi.org/10.1038/ng.2843

    Article  CAS  PubMed  Google Scholar 

  • Stewart SA, Weinberg RA (2000) Telomerase and human tumorigenesis. Semin Cancer Biol 10(6):399–406. https://doi.org/10.1006/scbi.2000.0339

    Article  CAS  PubMed  Google Scholar 

  • Su LY, Li XL, Shen L, Zhang Y, Zhao MM, Yin ZH, Su HY, Zhou BS (2014) Polymorphisms of TERT and CLPTM1L and the risk of hepatocellular carcinoma in Chinese males. Asian Pac J Cancer Prev 15(19):8197–8201. https://doi.org/10.7314/apjcp.2014.15.19.8197

    Article  PubMed  Google Scholar 

  • Trifa AP, Bănescu C, Tevet M, Bojan A, Dima D, Urian L, Török-Vistai T, Popov VM, Zdrenghea M, Petrov L, Vasilache A, Murat M, Georgescu D, Popescu M, Pătrinoiu O, Balea M, Costache R, Coleș E, Șaguna C, Berbec N, Vlădăreanu AM, Mihăilă RG, Bumbea H, Cucuianu A, Popp RA (2016) TERT rs2736100 A>C SNP and JAK2 46/1 haplotype significantly contribute to the occurrence of JAK2 V617F and CALR mutated myeloproliferative neoplasms—a multicentric study on 529 patients. Br J Haematol 174(2):218–226. https://doi.org/10.1111/bjh.14041

    Article  CAS  PubMed  Google Scholar 

  • Vaiciulis P, Liutkeviciene R, Liutkevicius V, Vilkeviciute A, Gedvilaite G, Uloza V (2020) association of relative leucocyte telomere length and gene single nucleotide polymorphisms (TERT, TRF1, TNKS2) in laryngeal squamous cell carcinoma. Cancer Genomics Proteomics 17(4):431–439. https://doi.org/10.21873/cgp.20202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Viana-Pereira M, Moreno DA, Linhares P, Amorim J, Nabiço R, Costa S, Vaz R (2020) Replication of GWAS identifies RTEL1, CDKN2A/B, and PHLDB1 SNPs as risk factors in Portuguese gliomas patients. Mol Biol Rep 47(2):877–886. https://doi.org/10.1007/s11033-019-05178-8

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Sun Y (2020) Telomerase reverse transcriptase rs2736098 polymorphism is associated with lung cancer: a meta-analysis. J Int Med Res. https://doi.org/10.1177/0300060520936173

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang S, Wu J, Hu L, Ding C, Kan Y, Shen Y, Chen X, Shen H, Guo X, Hu Z (2012) Common genetic variants in TERT contribute to risk of cervical cancer in a Chinese population. Mol Carcinog 51(Suppl 1):E118-122. https://doi.org/10.1002/mc.21872

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Fu P, Pang Y, Liu C, Shao Z, Zhu J, Li J, Wang T, Zhang X, Liu J (2014) TERT rs2736100T/G polymorphism upregulates interleukin 6 expression in non-small cell lung cancer especially in adenocarcinoma. Tumour Biol 35(5):4667–4672. https://doi.org/10.1007/s13277-014-1611-z

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Yang H, Feng T, Geng T, Chen C, Jin T (2016a) Effects of TERT gene polymorphism and environmental factor interactions on lung cancer risk in the Xi@ an Han population. Int J Clin Exp Med 9(2):4200–4210

    CAS  Google Scholar 

  • Wang X, Ma K, Chi L, Cui J, Jin L, Hu JF, Li W (2016b) Combining telomerase reverse transcriptase genetic variant rs2736100 with epidemiologic factors in the prediction of lung cancer susceptibility. J Cancer 7(7):846–853. https://doi.org/10.7150/jca.13437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei R, Cao L, Pu H, Wang H, Zheng Y, Niu X, Weng X, Zhang H, Favus M, Zhang L, Jia W, Zeng Y, Amos CI, Lu S, Wang HY, Liu Y, Liu W (2015) TERT polymorphism rs2736100-C is associated with EGFR mutation-positive non-small cell lung cancer. Clin Cancer Res 21(22):5173–5180. https://doi.org/10.1158/1078-0432.CCR-15-0009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu H, Qiao N, Wang Y, Jiang M, Wang S, Wang C, Hu L (2013) Association between the telomerase reverse transcriptase (TERT) rs2736098 polymorphism and cancer risk: evidence from a case–control study of non-small-cell lung cancer and a meta-analysis. PLoS ONE 8(11):e76372. https://doi.org/10.1371/journal.pone.0076372

    Article  PubMed  PubMed Central  Google Scholar 

  • Wysoczanska B, Dratwa M, Gebura K, Mizgala J, Mazur G, Wrobel T, Bogunia-Kubik K (2019) Variability within the human TERT gene, telomere length and predisposition to chronic lymphocytic leukemia. OncoTargets Ther 12:4309–4320. https://doi.org/10.2147/ott.S198313

    Article  CAS  Google Scholar 

  • Xiao X, He W (2017) Genetic polymorphisms in the TERT-CLPTM1L region and lung cancer susceptibility in Chinese males. Oncol Lett 14(2):1588–1594. https://doi.org/10.3892/ol.2017.6289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xing YL, Liu F, Li JF, Lin JC, Zhu GD, Li M, Zhang CR, Niu YY (2016) Case–control study on impact of the telomerase reverse transcriptase gene polymorphism and additional single nucleotide polymorphism (SNP)—SNP interaction on non-small cell lung cancers risk in Chinese Han population. J Clin Lab Anal 30(6):1071–1077. https://doi.org/10.1002/jcla.21982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yadav S, Chandra A, Kumar A, Mittal B (2018) Association of TERT-CLPTM1L and 8q24 common genetic variants with gallbladder cancer susceptibility and prognosis in north Indian population. Biochem Genet 56(4):267–282. https://doi.org/10.1007/s10528-018-9843-z

    Article  CAS  PubMed  Google Scholar 

  • Yin J, Wang L, Zheng L, Wang X, Shi Y, Shao A, Ding G, Liu C, Chen S, Tang W, Gu H (2014a) TERT-CLPTM1L Rs401681 C>T polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population. PLoS ONE 9(7):e100667. https://doi.org/10.1371/journal.pone.0100667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin Z, Cui Z, Ren Y, Zhang H, Yan Y, Zhao Y, Ma R, Wang Q, He Q, Zhou B (2014b) Genetic polymorphisms of TERT and CLPTM1L, cooking oil fume exposure, and risk of lung cancer: a case–control study in a Chinese non-smoking female population. Med Oncol 31(8):114. https://doi.org/10.1007/s12032-014-0114-5

    Article  CAS  PubMed  Google Scholar 

  • Yu J, Li X, Zhou B, Yan A (2019) Polymorphisms of the TERT-CLPTM1L Gene Are Associated with Pharynx–Larynx Cancer. DNA Cell Biol 38(9):915–921. https://doi.org/10.1089/dna.2019.4744

    Article  CAS  PubMed  Google Scholar 

  • Yuan X, Meng Y, Li P, Ge N, Kong F, Yang L, Björkholm M, Zhao S, Xu D (2016) The association between the TERT rs2736100 AC genotype and reduced risk of upper tract urothelial carcinomas in a Han Chinese population. Oncotarget 7(22):31972–31979. https://doi.org/10.18632/oncotarget.7777

    Article  PubMed  PubMed Central  Google Scholar 

  • Yuan X, Cheng G, Yu J, Zheng S, Sun C, Sun Q, Li K, Lin Z, Liu T, Li P, Xu Y, Kong F, Bjorkholm M, Xu D (2017) The TERT promoter mutation incidence is modified by germline TERT rs2736098 and rs2736100 polymorphisms in hepatocellular carcinoma. Oncotarget 8(14):23120–23129. https://doi.org/10.18632/oncotarget.15498

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang C, Tian YP, Wang Y, Guo FH, Qin JF, Ni H (2013) hTERT rs2736098 genetic variants and susceptibility of hepatocellular carcinoma in the Chinese population: a case–control study. Hepatobiliary Pancreat Dis Int 12(1):74–79. https://doi.org/10.1016/s1499-3872(13)60009-0

    Article  PubMed  Google Scholar 

  • Zhang Y, Zhao M, Shen L, Ren Y, Su L, Li X, Yin Z, Zhou B (2014) Genetic polymorphisms of TERT and CLPTM1L and risk of lung cancer: a case–control study in northeast Chinese male population. Med Oncol 31(7):18. https://doi.org/10.1007/s12032-014-0018-4

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Zhang X, Zhang H, Zhai Y, Wang Z, Li P, Yu L, Xia X, Zhang Y, Zeng Y, He F, Zhou G (2016) Common variations in TERT-CLPTM1L locus are reproducibly associated with the risk of nasopharyngeal carcinoma in Chinese populations. Oncotarget 7(1):759–770. https://doi.org/10.18632/oncotarget.6397

    Article  PubMed  Google Scholar 

  • Zhang J, Ju H, Gao JR, Jiao XL, Lu Y (2017) Polymorphisms in human telomerase reverse transcriptase (hTERT) gene, gene–gene and gene–smoking interaction with susceptibility to gastric cancer in Chinese Han population. Oncotarget 8(12):20235–20243. https://doi.org/10.18632/oncotarget.15664

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao MM, Zhang Y, Shen L, Ren YW, Li XL, Yin ZH, Zhou BS (2014) Genetic variations in TERT-CLPTM1L genes and risk of lung cancer in a Chinese population. Asian Pac J Cancer Prev 15(6):2809–2813. https://doi.org/10.7314/apjcp.2014.15.6.2809

    Article  PubMed  Google Scholar 

  • Zhou L, Fu G, Wei J, Shi J, Pan W, Ren Y, Xiong X, Xia J, Shen Y, Li H, Yang M (2016) The identification of two regulatory ESCC susceptibility genetic variants in the TERT-CLPTM1L loci. Oncotarget 7(5):5495–5506. https://doi.org/10.18632/oncotarget.6747

    Article  PubMed  Google Scholar 

  • Zhou M, Jiang B, Xiong M, Zhu X (2018) Association between TERT rs2736098 polymorphisms and cancer risk-a meta-analysis. Front Physiol 9:377. https://doi.org/10.3389/fphys.2018.00377

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by National Natural Science Foundation of China (81702686, 81602920), The young talents program of Jiangsu Cancer Hospital.

Funding

National Natural Science Foundation of China, Grant/Award Number: 81702686 and 81602920; Young Talents Program of Jiangsu Cancer Hospital.

Author information

Author notes

  1. Xinyu Zhang and Yan Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of The Sixth Dental Division, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, People’s Republic of China

    Xinyu Zhang, Donglin Yan & Longbiao Zhu

  2. Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, People’s Republic of China

    Xinyu Zhang, Donglin Yan & Longbiao Zhu

  3. Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China

    Xinyu Zhang, Donglin Yan & Longbiao Zhu

  4. Jiangsu Cancer Centre, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China

    Yan Chen & Jing Han

Authors
  1. Xinyu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Donglin Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jing Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Longbiao Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XZ and YC conducted the investigation by processing data and writing, DY checked data and results, JH was the project administration and supervised the project, LZ proposed the project, funded the project, and edited the writing.

Corresponding author

Correspondence to Longbiao Zhu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 64 kb)

Supplementary file2 (DOCX 50 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, X., Chen, Y., Yan, D. et al. TERT Gene rs2736100 and rs2736098 Polymorphisms are Associated with Increased Cancer Risk: A Meta-Analysis. Biochem Genet 60, 241–266 (2022). https://doi.org/10.1007/s10528-021-10097-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-021-10097-0

Keywords

Search

Navigation