Abstract
The rise in cancer survival rates has raised concerns about the long-term adverse effects of cancer treatment, including neurocognitive impairment. Neurocognitive deficits such as attention and processing speed are frequently observed and can have a profound, lifelong impact in daily life of cancer patients. Interestingly, large interpatient variability exists in cognitive outcomes. Emerging evidence indicates that such differences may be related to genetic variation. The aim of our review was to systematically summarize the current literature on the modulatory effects of germline genetic polymorphisms on cancer treatment-induced cognitive changes and the potential age-dependent impact in cancer survivors. The PubMed/Medline database was screened using an extensive search string focusing on four components: “cancer”, “cancer treatment”, “neurocognitive outcome” and “germline genetic variation”. Seventeen studies meeting predefined eligibility criteria were analyzed, including sixteen candidate gene studies and one genome-wide association study. 38 polymorphisms in 15 genes across proposed pathophysiological pathways, including (1) neural plasticity and repair, (2) neuroinflammation and defenses against oxidative stress, (3) neurotransmission, and (4) folate metabolism pathway, were reported to be significantly associated with treatment-related neurocognitive dysfunction or neuroimaging abnormalities. Still, some study results remained discordant, partly due to the methodological heterogeneity (i.e. in test assessments, age, cancer-type populations). Future large-scale, (epi-)genome studies integrating neurocognitive assessments and advanced neuroimaging techniques, are recommended in order to investigate neurotoxicity throughout the lifespan. Hence, adverse neurodevelopmental problems during childhood and neurodegenerative processes later in life could be minimized based on genetic risk classifications.
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Aerts, H., Fias, W., Caeyenberghs, K., & Marinazzo, D. (2016). Brain networks under attack: Robustness properties and the impact of lesions. Brain. https://doi.org/10.1093/brain/aww194
Ahles, T. A., Saykin, A. J., Noll, W. W., Furstenberg, C. T., Guerin, S., Cole, B., & Mott, L. A. (2003). The relationship of APOE genotype to neuropsychological performance in long-term cancer survivors treated with standard dose chemotherapy. Psycho-Oncology, 12(6), 612–619. https://doi.org/10.1002/pon.742
Ahles, T., Li, Y., McDonald, B., Schwartz, G., Kaufman, P., Tsongalis, G., et al. (2014). Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: the impact of APOE and smoking. Psycho-oncol., 23(12), 1382–1390 http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=ovftp&NEWS=N&AN=01445499-201412000-00007. Accessed 01 Dec 2015.
Alvim, R. O., Freitas, S. R., Ferreira, N. E., Santos, P. C., Cunha, R. S., Mill, J. G., et al. (2010). APOE polymorphism is associated with lipid profile, but not with arterial stiffness in the general population. Lipids in Health and Disease, 9(1), 128. https://doi.org/10.1186/1476-511X-9-128
American Cancer Society. (2015). Key statistics for childhood leukemia.
Amidi, A., Hosseini, S. M. H., Leemans, A., Kesler, S. R., Agerbæk, M., Wu, L. M., & Zachariae, R. (2017). Changes in Brain Structural Networks and Cognitive Functions in Testicular Cancer Patients Receiving Cisplatin-Based Chemotherapy. Journal of the National Cancer Institute, 109(12). https://doi.org/10.1093/jnci/djx085
Askins, M. A., Moore, B. D., III, & Moore, B. D. (2008). Preventing neurocognitive late effects in childhood cancer survivors. Journal of Child Neurology, 23(10), 1160–1171. https://doi.org/10.1016/j.biotechadv.2011.08.021.Secreted
Barahmani, N., Carpentieri, S., Li, X.-N., Wang, T., Cao, Y., Howe, L., et al. (2009). Glutathione S-transferase M1 and T1 polymorphisms may predict adverse effects after therapy in children with medulloblastoma. Neuro-oncology, 11(3), 292–300. https://doi.org/10.1215/15228517-2008-089
Barry, E., DeAngelo, D. J., Neuberg, D., Stevenson, K., Loh, M. L., Asselin, B. L., et al. (2007). Favorable outcome for adolescents with acute lymphoblastic leukemia treated on Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium protocols. Journal of Clinical Oncology, 25(7), 813–819. https://doi.org/10.1200/JCO.2006.08.6397
Bhojwani, D., Sabin, N. D., Pei, D., Yang, J. J., Khan, R. B., Panetta, J. C., et al. (2014). Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia. Journal of Clinical Oncology, 32(9), 949–959. https://doi.org/10.1200/JCO.2013.53.0808
Bilder, R. M., Volavka, J., Lachman, H. M., & Grace, A. A. (2004). The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes. Neuropsychopharmacology, 29(11), 1943–1961. https://doi.org/10.1038/sj.npp.1300542
Billiet, T., Vandenbulcke, M., Maedler, B., Peeters, R., Dhollander, T., Zhang, H., et al. (2015). Age-related microstructural differences quantified using myelin water imaging and advanced diffusion MRI. Neurobiology of Aging, 36(6), 2107–2121. https://doi.org/10.1016/j.neurobiolaging.2015.02.029
Brackett, J., Krull, K. R., Scheurer, M. E., Liu, W., Srivastava, D. K., Stovall, M., et al. (2012). Antioxidant enzyme polymorphisms and neuropsychological outcomes in medulloblastoma survivors: a report from the Childhood Cancer Survivor Study. Neuro-oncology, 14(8), 1018–1025. https://doi.org/10.1093/neuonc/nos123
Brouwers, P. (2005). Commentary: Study of the neurobehavioral consequences of childhood cancer: Entering the genomic era? Journal of Pediatric Psychology. https://doi.org/10.1093/jpepsy/jsi018
Buizer, A. I., de Sonneville, L. M. J., & Veerman, A. J. P. (2009). Effects of chemotherapy on neurocognitive function in children with acute lymphoblastic leukemia: a critical review of the literature. Pediatric Blood & Cancer, 52(4), 447–454. https://doi.org/10.1002/pbc.21869
Castellino, S. M., Ullrich, N. J., Whelen, M. J., & Lange, B. J. (2014). Developing interventions for cancer-related cognitive dysfunction in childhood cancer survivors. Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/dju186
Cheng, H., Li, W., Gan, C., Zhang, B., Jia, Q., & Wang, K. (2016). The COMT (rs165599) gene polymorphism contributes to chemotherapy-induced cognitive impairment in breast cancer patients. American Journal of Translational Research, 8(11), 5087–5097.
Cheung, Y. T., Khan, R. B., Liu, W., Brinkman, T. M., Edelmann, M. N., Reddick, W. E., et al. (2018). Association of Cerebrospinal Fluid Biomarkers of Central Nervous System Injury With Neurocognitive and Brain Imaging Outcomes in Children Receiving Chemotherapy for Acute Lymphoblastic Leukemia. JAMA Oncology, 38105, 1–8. https://doi.org/10.1001/jamaoncol.2018.0089
Cole, P. D. (2015). Does genetic susceptibility increase risk for neurocognitive decline among patients with acute lymphoblastic leukemia? Future Oncology, 11(13), 1855–1858. https://doi.org/10.2217/fon.15.117
Cole, P., Finkelstein, Y., Stevenson, K., Blonquist, T., Vijayanathan, V., Silverman, L., et al. (2015). Polymorphisms in Genes Related to Oxidative Stress Are Associated With Inferior Cognitive Function After Therapy for Childhood Acute Lymphoblastic Leukemia. Journal of Clinical Oncology : Official Journal of The American Society of Clinical Oncology, 33(19), 2205–2211. https://doi.org/10.1200/JCO.2014.59.0273
Correa, D. D., Cheung, K., Richards, E., Lin, M., Lyo, J., & Deangelis, L. M. (2014a). APOE polymorphisms and cognitive functions in patients with brain tumors, (November 2013).
Correa, D. D. D., Satagopan, J., Baser, R., Cheung, K., Richards, E., Lin, M., et al. (2014b). APOE polymorphisms and cognitive functions in patients with brain tumors. Neurology, 83(4), 320–327. https://doi.org/10.1212/WNL.0000000000000617
Correa, D. D., Satagopan, J., Cheung, K., Arora, A. K., Kryza-Lacombe, M., Xu, Y., et al. (2016). COMT, BDNF, and DTNBP1 polymorphisms and cognitive functions in patients with brain tumors. Neuro-oncology, 18(10), 1425–1433. https://doi.org/10.1093/neuonc/now057
Correa, D., DeAngelis, L., Shi, W., Thaler, H., Lin, M., & Abrey, L. (2007). Cognitive functions in low-grade gliomas: Disease and treatment effects. Journal of Neuro-Oncology, 81(2), 175–184. https://doi.org/10.1007/s11060-006-9212-3 http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L44963976%5Cn%5Cn cy7sh3vq3t.search.serialssolutions.com?sid=EMBASE&sid=EMBASE&issn=0167594X&id=&atitle=. Accessed 19 July 2006.
Cronstein, B. N., Naime, D., & Ostad, E. (1993). The antiinflammatory mechanism of methotrexate: Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. Journal of Clinical Investigation, 92(6), 2675–2682. https://doi.org/10.1172/JCI116884
Deprez, S., Kesler, S. R., Saykin, A. J., Silverman, D. H. S., de Ruiter, M. B., & McDonald, B. C. (2018). International Cognition and Cancer Task Force Recommendations for Neuroimaging Methods in the Study of Cognitive Impairment in Non-CNS Cancer Patients. JNCI: Journal of the National Cancer Institute, 110(3).
Dorus, S., Vallender, E. J., Evans, P. D., Anderson, J. R., Gilbert, S. L., Mahowald, M., et al. (2004). Accelerated evolution of nervous system genes in the origin of Homo sapiens. Cell, 119(7), 1027–1040. https://doi.org/10.1016/j.cell.2004.11.040
Duffner, P. K., Armstrong, F. D., Chen, L., Helton, K. J., Brecher, M. L., Bell, B., & Chauvenet, A. R. (2014). Neurocognitive and neuroradiologic central nervous system late effects in children treated on Pediatric Oncology Group (POG) P9605 (standard risk) and P9201 (lesser risk) acute lymphoblastic leukemia protocols (ACCL0131): a methotrexate consequence? A rep. Journal of Pediatric Hematology/Oncology, 36(1), 8–15. https://doi.org/10.1097/MPH.0000000000000000
Epstein, F. H., Lipton, S. A., & Rosenberg, P. A. (1994). Excitatory Amino Acids as a Final Common Pathway for Neurologic Disorders. New England Journal of Medicine, 330(9), 613–622. https://doi.org/10.1056/NEJM199403033300907
Ferguson, R. J., McDonald, B. C., Saykin, A. J., & Ahles, T. A. (2007). Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 25(25), 3866–3870. https://doi.org/10.1200/JCO.2007.10.8639
Ferreri, F., Lapp, L. K., & Peretti, C.-S. (2011). Current research on cognitive aspects of anxiety disorders. Current Opinion in Psychiatry, 24(1), 49–54. https://doi.org/10.1097/YCO.0b013e32833f5585
Finkelstein, J. D., & Martin, J. J. (1986). Methionine metabolism in mammals. Adaptation to methionine excess. Journal of Biological Chemistry, 261(4), 1582–1587. https://doi.org/10.1016/0955-2863(90)90070-2
Fjell, A. M., Grydeland, H., Krogsrud, S. K., Amlien, I., Rohani, D. A., Ferschmann, L., et al. (2015). Development and aging of cortical thickness correspond to genetic organization patterns. Proceedings of the National Academy of Sciences, 112(50), 15462–15467. https://doi.org/10.1073/pnas.1508831112
Fredholm, B. B., Chen, J. F., Cunha, R. A., Svenningsson, P., & Vaugeois, J. M. (2005). Adenosine and Brain Function. International Review of Neurobiology, 63, 191–270. https://doi.org/10.1016/S0074-7742(05)63007-3
Frosst, P., Blom, H. J., Milos, R., Goyette, P., Sheppard, C. A., Matthews, R. G., et al. (1995). A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genetics, 10(1), 111–113. https://doi.org/10.1038/ng0595-111
Garte, S., Gaspari, L., Alexandrie, A. K., Ambrosone, C., Autrup, H., Autrup, J. L., et al. (2001). Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiology, Biomarkers & Prevention : A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology, 10(12), 1239–1248.
Gershon, M. D., Sherman, D. L., & Pintar, J. E. (1990). Type-specific localization of monoamine oxidase in the enteric nervous system: Relationship to 5-hydroxytryptamine, neuropeptides, and sympathetic nerves. The Journal of Comparative Neurology, 301(2), 191–213. https://doi.org/10.1002/cne.903010205
Gilbert, S. L., Dobyns, W. B., & Lahn, B. T. (2005). Genetic links between brain development and brain evolution. Nature Reviews Genetics, 6(7), 581–590. https://doi.org/10.1038/nrg1634
Guo, A. Y., Sun, J., Riley, B. P., Thiselton, D. L., Kendler, K. S., & Zhao, Z. (2009). The dystrobrevin-binding protein 1 gene: features and networks. Molecular Psychiatry, 14(1), 18–29. https://doi.org/10.1038/mp.2008.88
Harrison, P. J., & Weinberger, D. R. (2005). Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Molecular Psychiatry, 10(1), 40–68. https://doi.org/10.1038/sj.mp.4001558
Hayes, J. D., Flanagan, J. U., & Jowsey, I. R. (2005). GLUTATHIONE TRANSFERASES. Annual Review of Pharmacology and Toxicology, 45(1), 51–88. https://doi.org/10.1146/annurev.pharmtox.45.120403.095857
Hodgson, K. D., Hutchinson, A. D., Wilson, C. J., & Nettelbeck, T. (2013). A meta-analysis of the effects of chemotherapy on cognition in patients with cancer. Cancer Treatment Reviews, 39(3), 297–304. https://doi.org/10.1016/j.ctrv.2012.11.001
Horie, N., Aiba, H., Oguro, K., Hojo, H., & Takeishi, K. (1995). Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5′-terminal regulatory region of the human gene for thymidylate synthase. Cell Structure and Function, 20(3), 191–197. https://doi.org/10.1247/csf.20.191
Howarth, R. A., Adamson, A. M., Ashford, J. M., Merchant, T. E., Ogg, R. J., Schulenberg, S. E., et al. (2014). Investigating the relationship between COMT polymorphisms and working memory performance among childhood brain tumor survivors. Pediatric Blood & Cancer, 61(1), 40–45. https://doi.org/10.1002/pbc.24649
Hunter, R. G., Gagnidze, K., McEwen, B. S., & Pfaff, D. W. (2014). Stress and the dynamic genome: Steroids, epigenetics, and the transposome. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1411260111
Jain, N., Brouwers, P., Okcu, M. F., Cirino, P. T., & Krull, K. R. (2009). Sex-specific attention problems in long-term survivors of pediatric acute lymphoblastic leukemia. Cancer, 115(18), 4238–4245. https://doi.org/10.1002/cncr.24464
Jorgensen, A. L., & Williamson, P. R. (2008). Methodological quality of pharmacogenetic studies: Issues of concern. Statistics in Medicine, 27(30), 6547–6569. https://doi.org/10.1002/sim.3420
Kamdar, K. Y., Krull, K. R., El-Zein, R. A., Brouwers, P., Potter, B. S., Harris, L. L., et al. (2011). Folate pathway polymorphisms predict deficits in attention and processing speed after childhood leukemia therapy. Pediatric Blood and Cancer, 57(3), 454–460. https://doi.org/10.1002/pbc.23162
Kennedy, J. L., Farrer, L. A., Andreasen, N. C., Mayeux, R., & St. George-Hyslop, P. (2003). The Genetics of Adult-Onset Neuropsychiatric Disease: Complexities and Conundra? Science. https://doi.org/10.1126/science.1092132
Kesler, S., Janelsins, M., Koovakkattu, D., Palesh, O., Mustian, K., Morrow, G., & Dhabhar, F. S. (2013a). Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors. Brain, Behavior, and Immunity, 30(SUPPL.), S109–16. https://doi.org/10.1016/j.bbi.2012.05.017
Kesler, S. R., Watson, C., Koovakkattu, D., Lee, C., O’Hara, R., Mahaffey, M. L., & Wefel, J. S. (2013b). Elevated prefrontal myo-inositol and choline following breast cancer chemotherapy. Brain Imaging and Behavior, 7(4), 501–510. https://doi.org/10.1007/s11682-013-9228-1
Kishi, T., Tanaka, Y., & Ueda, K. (2000). Evidence for hypomethylation in two children with acute lymphoblastic leukemia and leukoencephalopathy. Cancer, 89(4), 925–931. https://doi.org/10.1002/1097-0142(20000815)89:4<925::AID-CNCR28>3.0.CO;2-W
Koleck, T. A., Bender, C. M., Clark, B. Z., Ryan, C. M., Ghotkar, P., Brufsky, A., et al. (2017). An exploratory study of host polymorphisms in genes that clinically characterize breast cancer tumors and pretreatment cognitive performance in breast cancer survivors. Breast cancer (Dove Medical Press), 9, 95–110. https://doi.org/10.2147/BCTT.S123785
Krajinovic, M., Robaey, P., Chiasson, S., Lemieux-Blanchard, E., Rouillard, M., Primeau, M., et al. (2005). Polymorphisms of genes controlling homocysteine levels and IQ score following the treatment for childhood ALL. Pharmacogenomics, 6(3), 293–302. https://doi.org/10.1517/14622416.6.3.293
Krull, K. R., Bhojwani, D., Conklin, H. M., Pei, D., Cheng, C., Reddick, W. E., et al. (2013a). Genetic mediators of neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 31(17), 2182–2188. https://doi.org/10.1200/JCO.2012.46.7944
Krull, K. R., Brinkman, T. M., Li, C., Armstrong, G. T., Ness, K. K., Kumar Srivastava, D., et al. (2013b). Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: A report from the St jude lifetime cohort study. Journal of Clinical Oncology, 31(35), 4407–4415. https://doi.org/10.1200/JCO.2012.48.2315
Krull, K. R., Brouwers, P., Jain, N., Zhang, L., Bomgaars, L., Dreyer, Z., et al. (2008). Folate Pathway Genetic Polymorphisms are Related to Attention Disorders in Childhood Leukemia Survivors. Journal of Pediatrics, 152(1), 101–105. https://doi.org/10.1016/j.jpeds.2007.05.047
Lange, M., Rigal, O., Clarisse, B., Giffard, B., Sevin, E., Barillet, M., et al. (2014). Cognitive dysfunctions in elderly cancer patients: a new challenge for oncologists. Cancer Treatment Reviews, 40(6), 810–817. https://doi.org/10.1016/j.ctrv.2014.03.003
Leclerc, D., Campeau, E., Goyette, P., Adjalla, C. E., Christensen, B., Ross, M., et al. (1996). Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders. Human Molecular Genetics, 5(12), 1867–1874. https://doi.org/10.1093/hmg/5.12.1867
Lee, J. H. (2003). Genetic evidence for cognitive reserve: variations in memory and related cognitive functions. Journal of Clinical and Experimental Neuropsychology, 25(5), 594–613. https://doi.org/10.1076/jcen.25.5.594.14582
Linnebank, M., Homberger, A., Nowak-Göttl, U., Marquardt, T., Harms, E., & Koch, H. G. (2000). Linkage disequilibrium of the common mutations 677C > T and 1298A > C of the human methylenetetrahydrofolate reductase gene as proven by the novel polymorphisms 129C > T, 1068C > T. European Journal of Pediatrics, 159(6), 472–473. https://doi.org/10.1007/s004310051311
Linnebank, M., Moskau, S., Jürgens, A., Simon, M., Semmler, A., Orlopp, K., et al. (2009). Association of genetic variants of methionine metabolism with methotrexate-induced CNS white matter changes in patients with primary CNS lymphoma. Neuro-oncology, 11(1), 2–8. https://doi.org/10.1215/15228517-2008-082
Linnebank, M., Pels, H., Kleczar, N., Farmand, S., Fliessbach, K., Urbach, H., et al. (2005). MTX-induced white matter changes are associated with polymorphisms of methionine metabolism. Neurology, 64(5), 912–913. https://doi.org/10.1212/01.WNL.0000152840.26156.74
Loscalzo, J. (1996, July). The oxidant stress of hyperhomocyst(e)inemia. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI118776
Luciano, M., Miyajima, F., Lind, P. A., Bates, T. C., Horan, M., Harris, S. E., et al. (2009). Variation in the dysbindin gene and normal cognitive function in three independent population samples. Genes, Brain and Behavior, 8(2), 218–227. https://doi.org/10.1111/j.1601-183X.2008.00462.x
Mahley, R. W., & Huang, Y. (2012, December). Apolipoprotein E Sets the Stage: Response to Injury Triggers Neuropathology. Neuron. NIH Public Access. https://doi.org/10.1016/j.neuron.2012.11.020
Mattay, V. S., & Goldberg, T. E. (2004). Imaging genetic influences in human brain function. Current Opinion in Neurobiology. https://doi.org/10.1016/j.conb.2004.03.014
McAllister, T. W., Ahles, T. A., Saykin, A. J., Ferguson, R. J., McDonald, B. C., Lewis, L. D., et al. (2004). Cognitive effects of cytotoxic cancer chemotherapy: predisposing risk factors and potential treatments. Current Psychiatry Reports, 6(5), 364–371.
Merriman, J. D., Aouizerat, B. E., Langford, D. J., Cooper, B. A., Baggott, C. R., Cataldo, J. K., et al. (2014). Preliminary evidence of an association between an interleukin 6 promoter polymorphism and self-reported attentional function in oncology patients and their family caregivers. Biological Research for Nursing, 16(2), 152–159. https://doi.org/10.1177/1099800413479441
Meyer-Lindenberg, A., Nichols, T., Callicott, J. H., Ding, J., Kolachana, B. S., Buckholtz, J. W., et al. (2006). Impact of complex genetic variation in COMT on human brain function. Molecular Psychiatry, 11(9), 867–877. https://doi.org/10.1038/sj.mp.4001860
Miller, J. W., Selhub, J., & Joseph, J. A. (1996). Oxidative damage caused by free radicals produced during catecholamine autoxidation: Protective effects of O-methylation and melatonin. Free Radical Biology and Medicine, 21(2), 241–249. https://doi.org/10.1016/0891-5849(96)00033-0
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & Group, T. P. (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement (Reprinted from Annals of Internal Medicine). Physical Therapy, 89(9), 873–880. https://doi.org/10.1371/journal.pmed.1000097
Monje, M., Thomason, M. E., Rigolo, L., Wang, Y., Waber, D. P., Sallan, S. E., & Golby, A. J. (2013). Functional and structural differences in the hippocampus associated with memory deficits in adult survivors of acute lymphoblastic leukemia. Pediatric Blood and Cancer, 60(2), 293–300. https://doi.org/10.1002/pbc.24263
Moore, B. D., 3rd. (2005). Neurocognitive outcomes in survivors of childhood cancer. Journal of Pediatric Psychology, 30(1), 51–63.
Mrakotsky, C. M., Silverman, L. B., Dahlberg, S. E., Alyman, M. C. A., Sands, S. A., Queally, J. T., et al. (2011). Neurobehavioral side effects of corticosteroids during active treatment for acute lymphoblastic leukemia in children are age-dependent: Report from Dana-Farber Cancer Institute ALL Consortium Protocol 00–01. Pediatric Blood and Cancer, 57(3), 492–498. https://doi.org/10.1002/pbc.23060
Mulhern, R. K., & Palmer, S. L. (2003). Neurocognitive late effects in pediatric cancer. Current Problems in Cancer, 27(4), 177–197.
Mulhern, R. K., Palmer, S. L., Reddick, W. E., Glass, J. O., Kun, L. E., Taylor, J., et al. (2001). Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss. Journal of Clinical Oncology, 19(2), 472–479. https://doi.org/10.1200/JCO.2001.19.2.472
Nagatsu, T. (2004, January). Progress in Monoamine Oxidase (MAO) Research in Relation to Genetic Engineering. NeuroToxicology. https://doi.org/10.1016/S0161-813X(03)00085-8
Nappi, A. J., & Vass, E. (1998). Hydroxyl radical formation via iron-mediated Fenton chemistry is inhibited by methylated catechols. Biochimica et Biophysica Acta, 1425(1), 159–167.
Ng, T., Teo, S. M., Yeo, H. L., Shwe, M., Gan, Y. X., Cheung, Y. T., et al. (2016). Brain-derived neurotrophic factor genetic polymorphism (rs6265) is protective against chemotherapy-associated cognitive impairment in patients with early-stage breast cancer. Neuro-Oncology, 18(2), 244–251. https://doi.org/10.1093/neuonc/nov162
Park, Y., & Waldman, I. D. (2014). Influence of the COMT val108/158met polymorphism on continuous performance task indices. Neuropsychologia, 61(1), 45–55. https://doi.org/10.1016/j.neuropsychologia.2014.06.008
Quinn, C. T., Griener, J. C., Bottiglieri, T., Hyland, K., Farrow, A., & Kamen, B. A. (1997). Elevation of homocysteine and excitatory amino acid neurotransmitters in the CSF of children who receive methotrexate for the treatment of cancer. Journal of Clinical Oncology, 15(8), 2800–2806. https://doi.org/10.1200/JCO.1997.15.8.2800
Ricciotti, E., & FitzGerald, G. A. (2011). Prostaglandins and inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(5), 986–1000. https://doi.org/10.1161/ATVBAHA.110.207449
Ross, S., Anand, S. S., Joseph, P., & Paré, G. (2012). Promises and challenges of pharmacogenetics: an overview of study design, methodological and statistical issues. JRSM Cardiovascular Disease, 1(1), 1–13. https://doi.org/10.1258/cvd.2012.012001
Satz, P. (1993). Brain reserve capacity on symptom onset after brain injury: a formulation and review of evidence for threshold theory. Neuropsychologia, 7, 273–295.
Savitz, J., Solms, M., & Ramesar, R. (2006). The molecular genetics of cognition: Dopamine, COMT and BDNF. Genes, Brain and Behavior, 5(4), 311–328. https://doi.org/10.1111/j.1601-183X.2005.00163.x
Saykin, A. J., Ahles, T. A., & McDonald, B. C. (2003). Mechanisms of chemotherapy-induced cognitive disorders: neuropsychological, pathophysiological, and neuroimaging perspectives. Seminars in Clinical Neuropsychiatry, 8(4), 201–216.
Schlauch, D., Glass, K., Hersh, C. P., Silverman, E. K., & Quackenbush, J. (2017). Estimating drivers of cell state transitions using gene regulatory network models. BMC Systems Biology, 11(1). https://doi.org/10.1186/s12918-017-0517-y
Seigers, R., & Fardell, J. E. (2011). Neurobiological basis of chemotherapy-induced cognitive impairment: A review of rodent research. Neuroscience and Biobehavioral Reviews. https://doi.org/10.1016/j.neubiorev.2010.09.006
Silverman, D. H. S., Dy, C. J., Castellon, S. A., Lai, J., Pio, B. S., Abraham, L., et al. (2007). Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy. Breast Cancer Research and Treatment, 103(3), 303–311. https://doi.org/10.1007/s10549-006-9380-z
Small, B. J., Rawson, K. S., Walsh, E., Jim, H. S. L., Hughes, T. F., Iser, L., et al. (2011). Catechol-O-methyltransferase genotype modulates cancer treatment-related cognitive deficits in breast cancer survivors. Cancer, 117(7), 1369–1376. https://doi.org/10.1002/cncr.25685
Sofowora, G., Dishy, V., Xie, H. G., Imamura, H., Nishimi, Y., Morales, C. R., et al. (2001). In-vivo effects of Glu298Asp endothelial nitric oxide synthase polymorphism. Pharmacogenetics, 11(9), 809–814. https://doi.org/10.1097/00008571-200112000-00009
Stam, C. J. (2014). Modern network science of neurological disorders. Nature Reviews Neuroscience, 15(10), 683–695. https://doi.org/10.1038/nrn3801
Stiles, J., & Jernigan, T. L. (2010). The basics of brain development. Neuropsychology Review. https://doi.org/10.1007/s11065-010-9148-4
Stouten-Kemperman, M. M., de Ruiter, M. B., Koppelmans, V., Boogerd, W., Reneman, L., & Schagen, S. B. (2014). Neurotoxicity in breast cancer survivors ≥10 years post-treatment is dependent on treatment type. Brain Imaging and Behavior, 275–284. https://doi.org/10.1007/s11682-014-9305-0
Stover, P. J. (2004). Physiology of folate and vitamin B12 in health and disease. Nutrition Reviews, 62(6 Pt 2), S3–S12; discussion S13. https://doi.org/10.1301/nr.2004.jun.S3
Takimoto, C. (1996). New Antifolates: Pharmacology and Clinical Applications. The Oncologist, 1(1 & 2), 68–81.
Tang, T. T.-T., Yang, F., Chen, B.-S., Lu, Y., Ji, Y., Roche, K. W., & Lu, B. (2009). Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression. Proceedings of the National Academy of Sciences, 106(50), 21395–21400. https://doi.org/10.1073/pnas.0910499106
Tannock, I. F., Ahles, T. A., Ganz, P. A., & Van Dam, F. S. (2004). Cognitive impairment associated with chemotherapy for cancer: report of a workshop. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 22(11), 2233–2239. https://doi.org/10.1200/JCO.2004.08.094
Teixeira, A. L., Barbosa, I. G., Diniz, B. S., & Kummer, A. (2010). Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function. Biomarkers in Medicine, 4(6), 871–887. https://doi.org/10.2217/bmm.10.111
Thompson, P. M., Cannon, T. D., Narr, K. L., van Erp, T., Poutanen, V. P., Huttunen, M., et al. (2001). Genetic influences on brain structure. Nature Neuroscience, 4(12), 1253–1258. https://doi.org/10.1038/nn758
Trinh, B. N., Ong, C. N., Coetzee, G. A., Yu, M. C., & Laird, P. W. (2002). Thymidylate synthase: A novel genetic determinant of plasma homocysteine and folate levels. Human Genetics, 111(3), 299–302. https://doi.org/10.1007/s00439-002-0779-2
Tsujimoto, S. I., Yanagimachi, M., Tanoshima, R., Urayama, K. Y., Tanaka, F., Aida, N., et al. (2016). Influence of ADORA2A gene polymorphism on leukoencephalopathy risk in MTX-treated pediatric patients affected by hematological malignancies. Pediatric Blood and Cancer, 63(11), 1983–1989. https://doi.org/10.1002/pbc.26090
van der Put, N. M. J., Gabreëls, F., Stevens, E. M. B., Smeitink, J. A. M., Trijbels, F. J. M., Eskes, T. K. A. B., et al. (1998). A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? American Journal of Human Genetics, 62(5), 1044–1051. https://doi.org/10.1086/301825
van der Put, N. M., van der Molen, E. F., Kluijtmans, L. A., Heil, S. G., Trijbels, J. M., Eskes, T. K., et al. (1997). Sequence analysis of the coding region of human methionine synthase: relevance to hyperhomocysteinaemia in neural-tube defects and vascular disease. QJM : Monthly Journal of the Association of Physicians, 90(8), 511–517.
Vardy, J. L., Dhillon, H. M., Pond, G. R., Rourke, S. B., Bekele, T., Renton, C., et al. (2015). Cognitive Function in Patients With Colorectal Cancer Who Do and Do Not Receive Chemotherapy: A Prospective, Longitudinal, Controlled Study. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 33(34), 4085–4092. https://doi.org/10.1200/JCO.2015.63.0905
Vardy, J. L., Stouten-Kemperman, M. M., Pond, G., Booth, C. M., Rourke, S. B., Dhillon, H. M., et al. (2017). A mechanistic cohort study evaluating cognitive impairment in women treated for breast cancer. Brain Imaging and Behavior. https://doi.org/10.1007/s11682-017-9728-5
Vezmar, S., Schüsseler, P., Becker, A., Bode, U., & Jaehde, U. (2009). Methotrexate-associated alterations of the folate and methyl-transfer pathway in the CSF of all patients with and without symptoms of neurotoxicity. Pediatric Blood and Cancer, 52(1), 26–32. https://doi.org/10.1002/pbc.21827
Vijayraghavan, S., Wang, M., Birnbaum, S. G., Williams, G. V., & Arnsten, A. F. T. (2007). Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nature Neuroscience, 10(3), 376–384. https://doi.org/10.1038/nn1846
Von Castel-Dunwoody, K. M., Kauwell, G. P. A., Shelnutt, K. P., Vaughn, J. D., Griffin, E. R., Maneval, D. R., et al. (2005). Transcobalamin 776C-???G polymorphism negatively affects vitamin B-12 metabolism. American Journal of Clinical Nutrition, 81(6), 1436–1441.
Waber, D. P., Carpentieri, S. C., Klar, N., Silverman, L. B., Schwenn, M., Hurwitz, C. A., et al. (2000). Cognitive sequelae in children treated for acute lymphoblastic leukemia with dexamethasone or prednisone. Journal of Pediatric Hematology/Oncology, 22(3), 206–213.
Wefel, J. S., Noll, K. R., & Scheurer, M. E. (2016). Neurocognitive functioning and genetic variation in patients with primary brain tumors. The Lancet Oncology, 17(3), 97–108. https://doi.org/10.1016/S1470-2045(15)00380-0
Wefel, J. S., Vardy, J., Ahles, T., & Schagen, S. B. (2011). International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. The Lancet Oncology, 12(7), 703–708. https://doi.org/10.1016/S1470-2045(10)70294-1
Wolkowitz, O. M., Lupien, S. J., Bigler, E., Levin, R. B., & Canick, J. (2004). The “steroid dementia syndrome”: An unrecognized complication of glucocorticoid treatment. In In Annals of the New York Academy of Sciences (Vol. 1032, pp. 191–194). https://doi.org/10.1196/annals.1314.018
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Sleurs, C., Madoe, A., Lagae, L. et al. Genetic Modulation of Neurocognitive Development in Cancer Patients throughout the Lifespan: a Systematic Review. Neuropsychol Rev 29, 190–219 (2019). https://doi.org/10.1007/s11065-019-09399-3
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DOI: https://doi.org/10.1007/s11065-019-09399-3