Abstract
We hypothesized that the IL-1β-511 C>T polymorphism could be associated with the development of neurotoxicity and that it could be a possible biomarker to rate the risk of occurrence of neurotoxicity in cancer patients. Genomic DNA was extracted from 85 cancer patients: 49 received systemic chemotherapeutic treatment (CHT) and 36 patients did not receive it (No-CHT). All subjects were genotyped for the functionally active polymorphisms of IL-1β-511 C>T. We estimated neurotoxicity with the evaluation of neurological deficits. CHT patients showed erythrocytopenia, neurological deficit and a slight lowering of cognitive performance. The subgroup of patients carrying the CC genotype of the IL-1β-511 C>T gene showed lesser neurological deficits. In the context of cancer treatment, we suggested the potential value of IL-1β-511 C>T as genetic biomarkers to identify patients with higher risk to develop neurological deficits.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ahles TA, Saykin AJ, Furstenberg CT et al (2002) Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. J Clin Oncol 20:485–493. doi:10.1200/JCO.20.2.485
Arend WP (2002) The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev 13:323–340
Argyriou AA, Iconomou G, Kalofonos HP (2008a) Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood 112:1593–1599
Argyriou AA, Polychronopoulos P, Iconomou G et al (2008b) A review on oxaliplatin-induced peripheral nerve damage. Cancer Treat Rev 34:368–377
Argyriou AA, Bruna J, Marmiroli P, Cavaletti G (2012) Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. Crit Rev Oncol Hematol 82:51–77
Baudino B, D’agata F, Caroppo P et al (2012) The chemotherapy long-term effect on cognitive functions and brain metabolism in lymphoma patients. Q J Nucl Med Mol imaging 56:559–568
Bower JE, Ganz PA, Irwin MR et al (2013) Cytokine genetic variations and fatigue among patients with breast cancer. J Clin Oncol 31:1656–1661. doi:10.1200/JCO.2012.46.2143
Cavaletti G, Marmiroli P (2010) Chemotherapy-induced peripheral neurotoxicity. Nat Rev Neurol 6:657–666. doi:10.1517/14740338.3.6.535
Cavaletti G, Marmiroli P (2015) Chemotherapy-induced peripheral neurotoxicity. Curr Opin Neurol 28:500–507. doi:10.1097/WCO.0000000000000234
Cavaletti G, Cavalletti E, Oggioni N et al (2000) Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration. Neurotoxicology 21:389–393
Cavaletti G, Alberti P, Marmiroli P (2011) Chemotherapy-induced peripheral neurotoxicity in the era of pharmacogenomics. Lancet Oncol 12:1151–1161
Cavallone L, Bonafè M, Olivieri F et al (2003) The role of IL-1 gene cluster in longevity: a study in Italian population. Mech Ageing Dev 124:533–538
Cleeland CS, Bennett GJ, Dantzer R et al (2003) Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? a cytokine-immunologic model of cancer symptoms. Cancer 97:2919–2925. doi:10.1002/cncr.11382
del Rey A, Apkarian AV, Martina M, Besedovsky HO (2012) Chronic neuropathic pain-like behavior and brain-borne IL-1β. Ann N Y Acad Sci 1262:101–107. doi:10.1111/j.1749-6632.2012.06621.x
Déniz-Naranjo MC, Muñoz-Fernandez C, Alemany-Rodríguez MJ et al (2008) Cytokine IL-1 beta but not IL-1 alpha promoter polymorphism is associated with Alzheimer disease in a population from the Canary Islands, Spain. Eur J Neurol 15:1080–1084. doi:10.1111/j.1468-1331.2008.02252.x
Di Bona D, Plaia A, Vasto S et al (2008) Association between the interleukin-1beta polymorphisms and Alzheimer’s disease: a systematic review and meta-analysis. Brain Res Rev 59:155–163. doi:10.1016/j.brainresrev.2008.07.003
di Giovine FS, Takhsh E, Blakemore AI, Duff GW (1992) Single base polymorphism at -511 in the human interleukin-1 beta gene (IL1 beta). Hum Mol Genet 1:450. doi:10.1093/hmg/1.6.450
Dinarello CA (1994) The biological properties of interleukin-1. Eur Cytokine Netw 5:517–531
El-Omar EM, Carrington M, Chow WH et al (2000) Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404:398–402. doi:10.1038/35006081
Forlenza OV, Diniz BS, Talib LL et al (2009) Increased serum IL-1beta level in Alzheimer’s disease and mild cognitive impairment. Dement Geriatr Cogn Disord 28:507–512. doi:10.1159/000255051
Ganz PA, Bower JE, Kwan L et al (2013) Does tumor necrosis factor-alpha (TNF-α) play a role in post-chemotherapy cerebral dysfunction? Brain Behav Immun 30(Suppl):S99–S108. doi:10.1016/j.bbi.2012.07.015
Green EK, Harris JM, Lemmon H et al (2002) Are interleukin-1 gene polymorphisms risk factors or disease modifiers in AD? Neurology 58:1566–1568. doi:10.1212/WNL.58.10.1566
Griffin WS (2006) Inflammation and neurodegenerative diseases. Am ClinNutr 83:470S–474S
Grimaldi LM, Casadei VM, Ferri C et al (2000) Association of early-onset Alzheimer’s disease with an interleukin-1alpha gene polymorphism. Ann Neurol 47:361–365
Hall SK, Perregaux DG, Gabel CA et al (2004) Correlation of polymorphic variation in the promoter region of the interleukin-1β gene with secretion of interleukin-1β protein. Arthritis Rheum 50:1976–1983. doi:10.1002/art.20310
Hausheer FH, Schilsky RL, Bain S et al (2006) Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy. Semin Oncol 33:15–49
Henderson ST, Poirier J (2011) Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer’s disease; a randomized, double-blind, placebo-controlled study. BMC Med Genet 12:137
Huang D, Pirskanen R, Hjelmström P, Lefvert AK (1998) Polymorphisms in IL-1beta and IL-1 receptor antagonist genes are associated with myasthenia gravis. J Neuroimmunol 81:76–81
Huang D, Zheng C, Giscombe R et al (1999) Polymorphisms at -174 and in the 3′ flanking region of interleukin-6 (IL-6) gene in patients with myasthenia gravis. J Neuroimmunol 101:197–200. doi:10.1016/S0165-5728(99)00140-X
Inagaki M, Yoshikawa E, Matsuoka Y et al (2007) Smaller regional volumes of brain gray and white matter demonstrated in breat cancer survivors exposed to adjuvant chemotherapy. Cancer 109:146–156. doi:10.1002/cncr.22368
Licastro F, Pedrini S, Ferri C et al (2000) Gene polymorphism affecting alpha1-antichymotrypsin and interleukin-1 plasma levels increases Alzheimer’s disease risk. Ann Neurol 48:388–391
Miller RJ, Jung H, Bhangoo SK, White FA (2009) Cytokine and chemokine regulation of sensory neuron function. Handb Exp Pharmacol 194:417–449. doi:10.1007/978-3-540-79090-7_12
Miller BJ, Buckley P, Seabolt W et al (2011) Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 70:663–671. doi:10.1016/j.biopsych.2011.04.013
Natori A, Ogata T, Sumitani M et al (2015) Potential role of pNF-H, a biomarker of axonal damage in the central nervous system, as a predictive marker of chemotherapy-induced cognitive impairment. Clin Cancer Res 21:1348–1352. doi:10.1158/1078-0432.CCR-14-2775
Nicklin MJ, Weith A, Duff GW (1994) A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes. Genomics 19:382–384
O’Farrell E, MacKenzie J, Collins B (2013) Clearing the air: a review of our current understanding of “chemo fog”. Curr Oncol Rep 15:260–269. doi:10.1007/s11912-013-0307-7
Pettersson CAV, Sharma HS, Olsson Y (1990) Vascular permeability of spinal nerve roots. a study in the rat with evans blue and lanthanum as tracers. Acta Neuropathol 81:148–154. doi:10.1007/BF00334503
Pociot F, Mølvig J, Wogensen L et al (1992) A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest 22:396–402
Poli F, Nocco A, Berra S et al (2002) Allele frequencies of polymorphisms of TNFA, IL-6, IL-10 and IFNG in an Italian caucasian population. Eur J Immunogenet 29:237–240. doi:10.1046/j.1365-2370.2002.00303.x
Ren K, Torres R (2009) Role of interleukin-1beta during pain and inflammation. Brain Res Rev 60:57–64
Rothwell NJ, Strijbos PJ (1995) Cytokines in neurodegeneration and repair. Int J Dev Neurosci 13:179–185
Santtila S, Savinainen K, Hurme M (1998) Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol 47:195–198. doi:10.1046/j.1365-3083.1998.00300.x
Schäfers M, Sorkin L (2008) Effect of cytokines on neuronal excitability. NeurosciLett 437:188–193. doi:10.1016/j.neulet.2008.03.052
Seretny M, Currie GL, Sena ES et al (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Pain 155:2461–2470. doi:10.1016/j.pain.2014.09.020
Seripa D, Dobrina A, Margaglione M et al (2003) Relevance of interleukin-1 receptor antagonist intron-2 polymorphism in ischemic stroke. Cerebrovasc Dis 15:276–281. doi:10.1159/000069497
Shafia S, Dilafroze Sofi FA et al (2014) Rheumatoid arthritis and genetic variations in cytokine genes: a population-based study in Kashmir Valley. Immunol Invest 43:349–359. doi:10.3109/08820139.2013.879171
Skundric DS, Dai R, James J, Lisak RP (2002) Activation of IL-1 signaling pathway in schwann cells during diabetic neuropathy. Ann N Y Acad Sci 958:393–398
Smith EML, Beck SL, Cohen J (2008) The total neuropathy score: a tool for measuring chemotherapy-induced peripheral neuropathy. Oncol Nurs Forum 35:96–102. doi:10.1188/08.ONF.96-102
Smith JA, Das A, Ray SK, Banik NL (2012) Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res Bull 87:10–20. doi:10.1016/j.brainresbull.2011.10.004
Sommer C, Kress M (2004) Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett 361:184–187
Spinnler H, Tognoni G (1987) Standardizzazione e taratura italiana di test neuropsicologici
Stefanidis I, Kreuer K, Dardiotis E et al (2014) Association between the interleukin-1β gene (IL1B) C-511T polymorphism and the risk of diabetic nephropathy in type 2 diabetes: a candidate-gene association study. DNA Cell Biol 33:463–468. doi:10.1089/dna.2013.2204
Vezzani A, Viviani B (2015) Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability. Neuropharmacology 96:70–82. doi:10.1016/j.neuropharm.2014.10.02
Vichaya EG, Chiu GS, Krukowski K et al (2015) Mechanisms of chemotherapy-induced behavioral toxicities. Front Neurosci 9:131. doi:10.3389/fnins.2015.00131
Wang XM, Lehky TJ, Brell JM, Dorsey SG (2012) Discovering cytokines as targets for chemotherapy-induced painful peripheral neuropathy. Cytokine 59:3–9
Wang X-M, Walitt B, Saligan L et al (2015) Chemobrain: a critical review and causal hypothesis of link between cytokines and epigenetic reprogramming associated with chemotherapy. Cytokine 72:86–96. doi:10.1016/j.cyto.2014.12.006
Weisman D, Hakimian E, Ho GJ (2006) Interleukins, inflammation, and mechanisms of Alzheimer’s disease. Vitam Horm 74:505–530
Wilkes G (2007) Peripheral neuropathy related to chemotherapy. Semin Oncol Nurs 23:162–173. doi:10.1016/j.soncn.2007.05.001
Wilson AG, di Giovine FS, Blakemore AI, Duff GW (1992) Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product. Hum Mol Genet 1:353. doi:10.1093/hmg/1.5.353
Windebank AJ, Grisold W (2008) Chemotherapy-induced neuropathy. J Peripher Nerv Syst 13:27–46. doi:10.1111/j.1529-8027.2008.00156.x
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Additional information
E. Peila and F. D’Agata equally contributed to this work.
Rights and permissions
About this article
Cite this article
Peila, E., D’Agata, F., Caroppo, P. et al. Chemotherapy-Induced Neurotoxicity: Evidence of a Protective Role of CC Homozygosis in the Interleukin-1β Gene-511 C>T Polymorphism. Neurotox Res 30, 521–529 (2016). https://doi.org/10.1007/s12640-016-9637-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12640-016-9637-1