Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Neuroblastoma | Research

RTEL1 gene polymorphisms and neuroblastoma risk in Chinese children

Authors: Ting Zhang, Chunlei Zhou, Jiejie Guo, Jiamin Chang, Haiyan Wu, Jing He

Published in: BMC Cancer | Issue 1/2023

Login to get access

Abstract

Background

Neuroblastoma, a neuroendocrine tumor originating from the sympathetic ganglia, is one of the most common malignancies in childhood. RTEL1 is critical in many fundamental cellular processes, such as DNA replication, DNA damage repair, genomic integrity, and telomere stability. Single nucleotide polymorphisms (SNPs) in the RTEL1 gene have been reported to confer susceptibility to multiple cancers, but their contributing roles in neuroblastoma remain unclear.

Methods

We conducted a study on 402 neuroblastoma cases and 473 controls to assess the association between four RTEL1 SNPs (rs3761124 T>C, rs3848672 T>C, rs3208008 A>C and rs2297441 G>A) and neuroblastoma susceptibility.

Results

Our results show that rs3848672 T>C is significantly associated with an increased risk of neuroblastoma [CC vs. TT/TC: adjusted odds ratio (OR)=1.39, 95% confidence interval (CI)=1.02-1.90, P=0.038]. The stratified analysis further indicated that boy carriers of the rs3848672 CC genotype had a higher risk of neuroblastoma, and all carriers had an increased risk of developing neuroblastoma of mediastinum origin. Moreover, the rs2297441 AA genotype increased neuroblastoma risk in girls and predisposed children to neuroblastoma arising from retroperitoneal.

Conclusion

Our study indicated that the rs3848672 CC and rs2297441 AA genotypes of the RTEL1 gene are significantly associated with an increased risk of neuroblastoma in Chinese children in a gender- and site-specific manner.
Appendix
Available only for authorised users
Literature
1.
Ivanova E, Sharma SD, Brichkina A, Pfefferle P, Keber U, Pagenstecher A, et al. DYRK3 contributes to differentiation and hypoxic control in neuroblastoma. Biochem Biophys Res Commun. 2021;567:215–21.PubMedCrossRef
2.
Bao PP, Li K, Wu CX, Huang ZZ, Wang CF, Xiang YM, et al. Recent incidences and trends of childhood malignant solid tumors in Shanghai, 2002-2010. Zhonghua Er Ke Za Zhi. 2013;51:288–94.PubMed
3.
4.
Morgenstern DA, Bagatell R, Cohn SL, Hogarty MD, Maris JM, Moreno L, et al. The challenge of defining “ultra-high-risk” neuroblastoma. Pediatr Blood Cancer. 2019;66:e27556.PubMedCrossRef
5.
Nakagawara A, Li Y, Izumi H, Muramori K, Inada H, Nishi M. Neuroblastoma. Jpn J Clin Oncol. 2018;48:214–41.PubMedCrossRef
6.
Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol. 2009;27:289–97.PubMedPubMedCentralCrossRef
7.
Han JZR, Hastings JF, Phimmachanh M, Fey D, Kolch W, Croucher DR. Personalized Medicine for Neuroblastoma: Moving from Static Genotypes to Dynamic Simulations of Drug Response. J Pers Med. 2021;11:395.PubMedPubMedCentralCrossRef
8.
Matthay KK, Maris JM, Schleiermacher G, Nakagawara A, Mackall CL, Diller L, et al. Neuroblastoma. Nat Rev Dis Primers. 2016;2:16078.PubMedCrossRef
9.
10.
Gatta G, Botta L, Rossi S, Aareleid T, Bielska-Lasota M, Clavel J, et al. Childhood cancer survival in Europe 1999–2007: results of EUROCARE-5–a population-based study. Lancet Oncol. 2014;15:35–47.PubMedCrossRef
11.
Ward E, DeSantis C, Robbins A, Kohler B, Jemal A. Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin. 2014;64:83–103.PubMedCrossRef
12.
Zheng R, Peng X, Zeng H, Zhang S, Chen T, Wang H, et al. Incidence, mortality and survival of childhood cancer in China during 2000–2010 period: A population-based study. Cancer Lett. 2015;363:176–80.PubMedCrossRef
13.
Westerveld ASR, van Dalen EC, Asogwa OA, Koopman MMW, Papadakis V, Laureys G, et al. Neuroblastoma survivors at risk for developing subsequent neoplasms: A systematic review. Cancer Treat Rev. 2022;104:102355.PubMedCrossRef
14.
Mosse YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008;455:930–5.PubMedPubMedCentralCrossRef
15.
Cook MN, Olshan AF, Guess HA, Savitz DA, Poole C, Blatt J, et al. Maternal medication use and neuroblastoma in offspring. Am J Epidemiol. 2004;159:721–31.PubMedCrossRef
16.
Consortium IHGS. Finishing the euchromatic sequence of the human genome. Science. 1984;224:1121–4.
17.
Aygun N. Biological and Genetic Features of Neuroblastoma and Their Clinical Importance. Curr Pediatr Rev. 2018;14:73–90.PubMedCrossRef
18.
Brodeur GM, Seeger RC, Schwab M, et al. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. 1984;224:1121–4.PubMedCrossRef
19.
van Limpt V, Schramm A, van Lakeman A, Sluis P, Chan A, van Noesel M, et al. The Phox2B homeobox gene is mutated in sporadic neuroblastomas. Oncogene. 2004;23:9280–8.PubMedCrossRef
20.
Diskin SJ, Capasso M, Diamond M, Oldridge DA, Conkrite K, Bosse KR, et al. Rare variants in TP53 and susceptibility to neuroblastoma. J Natl Cancer Inst. 2014;106:dju047.PubMedPubMedCentralCrossRef
21.
Russell MR, Penikis A, Oldridge DA, Alvarez-Dominguez JR, McDaniel L, Diamond M, et al. CASC15-S Is a Tumor Suppressor lncRNA at the 6p22 Neuroblastoma Susceptibility Locus. Cancer Res. 2015;75:3155–66.PubMedPubMedCentralCrossRef
22.
He J, Zou Y, Wang T, Zhang R, Yang T, Zhu J, et al. Genetic Variations of GWAS-Identified Genes and Neuroblastoma Susceptibility: a Replication Study in Southern Chinese Children. Transl Oncol. 2017;10:936–41.PubMedPubMedCentralCrossRef
23.
Molenaar JJ, Domingo-Fernandez R, Ebus ME, Lindner S, Koster J, Drabek K, et al. LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet. 2012;44:1199–206.PubMedCrossRef
24.
Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, et al. Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature. 2015;526:700–4.PubMedPubMedCentralCrossRef
25.
Cheung NK, Zhang J, Lu C, Parker M, Bahrami A, Tickoo SK, et al. Association of age at diagnosis and genetic mutations in patients with neuroblastoma. JAMA. 2012;307:1062–71.PubMedPubMedCentralCrossRef
26.
Wang K, Diskin SJ, Zhang H, Attiyeh EF, Winter C, Hou C, et al. Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature. 2011;469:216–20.PubMedCrossRef
27.
Diskin SJ, Hou C, Glessner JT, Attiyeh EF, Laudenslager M, Bosse K, et al. Copy number variation at 1q21.1 associated with neuroblastoma. Nature. 2009;459:987–91.PubMedPubMedCentralCrossRef
28.
Capasso M, Devoto M, Hou C, Asgharzadeh S, Glessner JT, Attiyeh EF, et al. Common variations in BARD1 influence susceptibility to high-risk neuroblastoma. Nat Genet. 2009;41:718–23.PubMedPubMedCentralCrossRef
29.
Chang X, Liu Y, Glessner J, Hou C, Qu H, Nguyen K, et al. Identification of Mitochondrial DNA Variants Associated With Risk of Neuroblastoma. J Natl Cancer Inst. 2022;114:910–3.PubMedPubMedCentralCrossRef
30.
Barber LJ, Youds JL, Ward JD, McIlwraith MJ, O’Neil NJ, Petalcorin MIR, et al. RTEL1 Maintains Genomic Stability by Suppressing Homologous Recombination. Cell. 2008;135:261–71.PubMedPubMedCentralCrossRef
31.
Ding H, Schertzer M, Wu X, Gertsenstein M, Selig S, Kammori M, et al. Regulation of murine telomere length by Rtel: an essential gene encoding a helicase-like protein. Cell. 2004;117:873–86.PubMedCrossRef
32.
Namgoong S, Cheong HS, Kim JH, Kim LH, Seo JY, Kang SG, et al. Association analysis of RTEL1 variants with risk of adult gliomas in a Korean population. PLoS One. 2018;13:e0207660.PubMedPubMedCentralCrossRef
33.
Yan S, Xia R, Jin T, Ren H, Yang H, Li J, et al. RTEL1 polymorphisms are associated with lung cancer risk in the Chinese Han population. Oncotarget. 2016;7:70475–80.PubMedPubMedCentralCrossRef
34.
Jin T, Wang Y, Li G, Du S, Yang H, Geng T, et al. Analysis of difference of association between polymorphisms in the XRCC5, RPA3 and RTEL1 genes and glioma, astrocytoma and glioblastoma. Am J Cancer Res. 2015;5:2294–300.PubMedPubMedCentral
35.
Lu S, Zhong J, Wu M, Huang K, Zhou Y, Zhong Z, et al. Genetic analysis of the relation of telomere length-related gene (RTEL1) and coronary heart disease risk. Mol Genet Genomic Med. 2019;7:e550.PubMedPubMedCentralCrossRef
36.
Yuan ZZ, Fan LL, Wang CY, Luo H, Liu L. Novel heterozygous mutation of RTEL1 in interstitial pneumonia with autoimmune feature. QJM. 2022;115:253–5.PubMedCrossRef
37.
Ziv A, Werner L, Konnikova L, Awad A, Jeske T, Hastreiter M, et al. An RTEL1 Mutation Links to Infantile-Onset Ulcerative Colitis and Severe Immunodeficiency. J Clin Immunol. 2020;40:1010–9.PubMedCrossRef
38.
Lin L, Deng C, Zhou C, Zhang X, Zhu J, Liu J, et al. NSUN2 gene rs13181449 C>T polymorphism reduces neuroblastoma risk. Gene. 2023;854:147120.PubMedCrossRef
39.
Chang J, Lin L, Zhou C, Zhang X, Yang T, Wu H, et al. Functional polymorphisms of the TET1 gene increase the risk of neuroblastoma in Chinese children. J Cell Mol Med. 2023;27:2239–48.PubMedPubMedCentralCrossRef
40.
He J, Yuan L, Lin H, Lin A, Chen H, Luo A, et al. Genetic variants in m(6)A modification core genes are associated with glioma risk in Chinese children. Mol Ther Oncolytics. 2021;20:199–208.PubMedPubMedCentralCrossRef
41.
Chen YP, Liao YX, Zhuo ZJ, Yuan L, Lin HR, Miao L, et al. Association between genetic polymorphisms of base excision repair pathway and glioma susceptibility in Chinese children. World J Pediatr. 2022;18:632–5.PubMedCrossRef
42.
Guan Q, Lin H, Hua W, Lin L, Liu J, Deng L, et al. Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression. Chin J Cancer Res. 2023;35:140–62.PubMedPubMedCentralCrossRef
43.
Machiela MJ, Chanock SJ. LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics. 2015;31:3555–7.PubMedPubMedCentralCrossRef
44.
45.
Vannier JB, Sarek G, Boulton SJ. RTEL1: functions of a disease-associated helicase. Trends Cell Biol. 2014;24:416–25.PubMedCrossRef
46.
Youds J L, Mets D G, McIlwraith M J, Martin J S, Ward J D, Oneil N J, et al. RTEL-1 Enforces Meiotic Crossover Interference and Homeostasis. Science. 2010;327:1254–8.PubMedPubMedCentralCrossRef
47.
Wang RC, Smogorzewska A, de Lange T. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell. 2004;119:355–68.PubMedCrossRef
48.
Wu X, Sandhu S, Nabi Z, Ding H. Generation of a mouse model for studying the role of upregulated RTEL1 activity in tumorigenesis. Transgenic Res. 2012;21:1109–15.PubMedPubMedCentralCrossRef
49.
Muleris M, Almeida A, Gerbault-Seureau M, Malfoy B, Dutrillaux B. Identification of amplified DNA sequences in breast cancer and their organization within homogeneously staining regions. Genes Chromosomes Cancer. 1995;14:155–63.PubMedCrossRef
50.
Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B, et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet. 2009;41:899–904.PubMedPubMedCentralCrossRef
51.
Egan KM, Thompson RC, Nabors LB, Olson JJ, Brat DJ, Larocca RV, et al. Cancer susceptibility variants and the risk of adult glioma in a US case-control study. J Neurooncol. 2011;104:535–42.PubMedPubMedCentralCrossRef
52.
Viana-Pereira M, Moreno DA, Linhares P, Amorim J, Nabico R, Costa S, et al. Replication of GWAS identifies RTEL1, CDKN2A/B, and PHLDB1 SNPs as risk factors in Portuguese gliomas patients. Mol Biol Rep. 2020;47:877–86.PubMedCrossRef
Metadata
Title
RTEL1 gene polymorphisms and neuroblastoma risk in Chinese children
Authors
Ting Zhang
Chunlei Zhou
Jiejie Guo
Jiamin Chang
Haiyan Wu
Jing He
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11642-3

Other articles of this Issue 1/2023

BMC Cancer 1/2023 Go to the issue

Research

Biological evaluation of novel gemcitabine analog in patient-derived xenograft models of pancreatic cancer

Research

FOLFOX regimen after failure of fluorouracil and leucovorin plus nanoliposomal-irinotecan therapy for advanced pancreatic cancer: a retrospective observational study

Research

Delay in diagnosis and associated factors among children with cancer admitted at pediatric oncology ward, University of Gondar comprehensive specialized hospital, Ethiopia: a retrospective cross-sectional study

Research

Investigating the functional role of SETD6 in lung adenocarcinoma

Research

The potential of high-order features of routine blood test in predicting the prognosis of non-small cell lung cancer

Research

Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits