Top

Published in:

01-03-2014 | Research Article

Association of BCL2-938C>A genetic polymorphism with glioma risk in Chinese Han population

Authors: Wei Li, Chunfa Qian, Linxiong Wang, Hong Teng, Li Zhang

Published in: Tumor Biology | Issue 3/2014

Abstract

Glioma is the most common type of primary brain malignancy in adults. The anti-apoptotic protein B-cell lymphoma 2 (BCL2) has been implicated in the pathogenesis of glioma. This study aimed to evaluate the potential association between BCL2-938C>A genetic polymorphism and glioma susceptibility. This case–control study was conducted in Chinese Han populations consisting of 248 glioma cases and 252 cancer-free controls. The BCL2-938C>A genetic polymorphism was detected by the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and verified using DNA sequencing methods. Our data suggested that the genotype/allele of BCL2-938C>A polymorphism were statistically associated with the increased risk of glioma where the risk of glioma for genotype AA or allele A is significantly higher than wild genotype CC (odds ratio (OR) = 2.23, 95 % confidence interval (CI) 1.21–4.10, p = 0.009) or allele C (OR = 1.39, 95 % CI 1.06–1.82, p = 0.016), respectively. In addition, the BCL2-938AA genotype was significantly more common in patients with glioblastoma and in patients with grade IV glioma. Our findings indicate that the BCL2-938C>A polymorphism is associated with the susceptibility to glioma in Chinese Han populations and might be used as molecular markers for evaluating glioma risk.

Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M. Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol. 2006;2(9):494–503. doi:10.1038/ncpneuro0289.PubMedCrossRef

Bondy ML, Scheurer ME, Malmer B, Barnholtz-Sloan JS, Davis FG, Il'yasova D, et al. Brain tumor epidemiology: consensus from the brain tumor epidemiology consortium. Cancer. 2008;113(7 Suppl):1953–68. doi:10.1002/cncr.23741.PubMedCentralPubMedCrossRef

Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre JY. Primary brain tumours in adults. Lancet. 2012;379(9830):1984–96. doi:10.1016/S0140-6736(11)61346-9.PubMedCrossRef

Ohgaki H, Kleihues P. Epidemiology and etiology of gliomas. Acta Neuropathol. 2005;109(1):93–108. doi:10.1007/s00401-005-0991-y.PubMedCrossRef

Samkange-Zeeb F, Schlehofer B, Schuz J, Schlaefer K, Berg-Beckhoff G, Wahrendorf J, et al. Occupation and risk of glioma, meningioma and acoustic neuroma: results from a German case–control study (interphone study group, Germany). Cancer Epidemiol. 2010;34(1):55–61. doi:10.1016/j.canep.2009.12.003.PubMedCrossRef

De Roos AJ, Stewart PA, Linet MS, Heineman EF, Dosemeci M, Wilcosky T, et al. Occupation and the risk of adult glioma in the United States. Cancer Causes Control : CCC. 2003;14(2):139–50.PubMedCrossRef

Maker HS, Syed H, Whetsell W, Lehrer GM. Environmental factors modifying the effect of CCNU on glioma in vitro and in vivo. Trans Am Neurol Assoc. 1976;101:273–5.PubMed

Bunin GR, Kuijten RR, Boesel CP, Buckley JD, Meadows AT. Maternal diet and risk of astrocytic glioma in children: a report from the childrens cancer group (United States and Canada). Cancer Causes Control : CCC. 1994;5(2):177–87.PubMedCrossRef

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(8):899–904. doi:10.1038/ng.407.PubMedCrossRef

10.

Wrensch M, Jenkins RB, Chang JS, Yeh RF, Xiao Y, Decker PA, et al. Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet. 2009;41(8):905–8. doi:10.1038/ng.408.PubMedCentralPubMedCrossRef

11.

Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2(9):647–56. doi:10.1038/nrc883.PubMedCrossRef

12.

Zinkel S, Gross A, Yang E. BCL2 family in DNA damage and cell cycle control. Cell Death Differ. 2006;13(8):1351–9. doi:10.1038/sj.cdd.4401987.PubMedCrossRef

13.

Faderl S, Keating MJ, Do KA, Liang SY, Kantarjian HM, O'Brien S, et al. Expression profile of 11 proteins and their prognostic significance in patients with chronic lymphocytic leukemia (CLL). Leuk Off J Leuk Soc Am Leuk Res Fund UK. 2002;16(6):1045–52. doi:10.1038/sj.leu.2402540.CrossRef

14.

Nuckel H, Frey UH, Bau M, Sellmann L, Stanelle J, Durig J, et al. Association of a novel regulatory polymorphism (−938C>A) in the BCL ₂ gene promoter with disease progression and survival in chronic lymphocytic leukemia. Blood. 2007;109(1):290–7. doi:10.1182/blood-2006-03-007567.PubMedCrossRef

15.

Bachmann HS, Heukamp LC, Schmitz KJ, Hilburn CF, Kahl P, Buettner R, et al. Regulatory BCL2 promoter polymorphism (−938C>A) is associated with adverse outcome in patients with prostate carcinoma. Int J Cancer J Int du Cancer. 2011;129(10):2390–9. doi:10.1002/ijc.25904.CrossRef

16.

Bachmann HS, Otterbach F, Callies R, Nuckel H, Bau M, Schmid KW, et al. The AA genotype of the regulatory BCL2 promoter polymorphism (938C>A) is associated with a favorable outcome in lymph node negative invasive breast cancer patients. Clin Cancer Res Off J Am Assoc Cancer Res. 2007;13(19):5790–7. doi:10.1158/1078-0432.CCR-06-2673.CrossRef

17.

Thomadaki H, Talieri M, Scorilas A. Prognostic value of the apoptosis related genes BCL2 and BCL2L12 in breast cancer. Cancer Lett. 2007;247(1):48–55. doi:10.1016/j.canlet.2006.03.016.PubMedCrossRef

18.

Lehnerdt GF, Franz P, Bankfalvi A, Grehl S, Kelava A, Nuckel H, et al. The regulatory BCL2 promoter polymorphism (−938C>A) is associated with relapse and survival of patients with oropharyngeal squamous cell carcinoma. Ann Oncol Off J Eur Soc Med Oncol ESMO. 2009;20(6):1094–9. doi:10.1093/annonc/mdn763.CrossRef

19.

Pena JC, Thompson CB, Recant W, Vokes EE, Rudin CM. Bcl-xL and Bcl-2 expression in squamous cell carcinoma of the head and neck. Cancer. 1999;85(1):164–70.PubMedCrossRef

20.

Seto M, Jaeger U, Hockett RD, Graninger W, Bennett S, Goldman P, et al. Alternative promoters and exons, somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma. EMBO J. 1988;7(1):123–31.PubMedCentralPubMed

21.

Young RL, Korsmeyer SJ. A negative regulatory element in the bcl-2 5'-untranslated region inhibits expression from an upstream promoter. Mol Cell Biol. 1993;13(6):3686–97.PubMedCentralPubMed

22.

Heubner M, Wimberger P, Otterbach F, Kasimir-Bauer S, Siffert W, Kimmig R, et al. Association of the AA genotype of the BCL2 (−938C>A) promoter polymorphism with better survival in ovarian cancer. Int J Biol Markers. 2009;24(4):223–9.PubMed

23.

Hirata H, Hinoda Y, Nakajima K, Kikuno N, Suehiro Y, Tabatabai ZL, et al. The bcl2-938CC genotype has poor prognosis and lower survival in renal cancer. J Urol. 2009;182(2):721–7. doi:10.1016/j.juro.2009.03.081.PubMedCrossRef

24.

Chen K, Hu Z, Wang LE, Sturgis EM, El-Naggar AK, Zhang W, et al. Single-nucleotide polymorphisms at the TP53-binding or responsive promoter regions of BAX and BCL2 genes and risk of squamous cell carcinoma of the head and neck. Carcinogenesis. 2007;28(9):2008–12. doi:10.1093/carcin/bgm172.PubMedCrossRef

25.

El Hindy N, Bachmann HS, Lambertz N, Adamzik M, Nuckel H, Worm K, et al. Association of the CC genotype of the regulatory BCL2 promoter polymorphism (−938C>A) with better 2-year survival in patients with glioblastoma multiforme. J Neurosurg. 2011;114(6):1631–9. doi:10.3171/2010.12.JNS10478.PubMedCrossRef

26.

Thurnher MM. 2007 World Health Organization classification of tumours of the central nervous system. Cancer imaging : the official publication of the International Cancer Imaging Society. 2009;9 Spec No A:S1-3. doi:10.1102/1470-7330.2009.9001.

27.

Kidd LR, Coulibaly A, Templeton TM, Chen W, Long LO, Mason T, et al. Germline BCL-2 sequence variants and inherited predisposition to prostate cancer. Prostate Cancer Prostatic Dis. 2006;9(3):284–92. doi:10.1038/sj.pcan.4500884.PubMedCrossRef

28.

Liu Z, Sun R, Lu W, Dang C, Song Y, Wang C, et al. The -938A/A genotype of BCL2 gene is associated with esophageal cancer. Med Oncol. 2012;29(4):2677–83. doi:10.1007/s12032-011-0135-2.PubMedCrossRef

29.

Masago K, Togashi Y, Fujita S, Nagai H, Sakamori Y, Okuda C, et al. Effect of the BCL2 gene polymorphism on survival in advanced-stage non-small cell lung cancer patients who received chemotherapy. Oncology. 2013;84(4):214–8. doi:10.1159/000342854.PubMedCrossRef

30.

Hirata H, Hinoda Y, Kikuno N, Suehiro Y, Shahryari V, Ahmad AE, et al. Bcl2–938C/A polymorphism carries increased risk of biochemical recurrence after radical prostatectomy. J Urol. 2009;181(4):1907–12. doi:10.1016/j.juro.2008.11.093.PubMedCrossRef

31.

Weller M, Malipiero U, Aguzzi A, Reed JC, Fontana A. Protooncogene bcl-2 gene transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation. J Clin Invest. 1995;95(6):2633–43. doi:10.1172/JCI117965.PubMedCentralPubMedCrossRef

32.

Newcomb EW, Bhalla SK, Parrish CL, Hayes RL, Cohen H, Miller DC. Bcl-2 protein expression in astrocytomas in relation to patient survival and p53 gene status. Acta Neuropathol. 1997;94(4):369–75.PubMedCrossRef

Title: Association of BCL2-938C>A genetic polymorphism with glioma risk in Chinese Han population
Authors: Wei Li
Chunfa Qian
Linxiong Wang
Hong Teng
Li Zhang
Publication date: 01-03-2014
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 3/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-013-1299-5

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2014

Association between TP53 Arg72Pro polymorphism and thyroid carcinoma risk

Feasibility and safety of carboplatin plus paclitaxel as neoadjuvant chemotherapy for locally advanced cervical cancer: a pilot study

XRCC3 Thr241Met polymorphism and ovarian cancer risk: a meta-analysis

Human kallikrein 2 (KLK2) promotes prostate cancer cell growth via function as a modulator to promote the ARA70-enhanced androgen receptor transactivation

Promoter hypermethylation of p14 ARF , RB, and INK4 gene family in hepatocellular carcinoma with hepatitis B virus infection

Significant associations between X-ray repair cross-complementing group 3 genetic polymorphisms and thyroid cancer risk

Keynote webinar | Spotlight on antibody–drug conjugates in cancer