Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Die Folgen des Klimwandels haben einen direkten Einfluss auf die Primärversorgung in Deutschland: Hitzeschutz insbesondere bei älteren Patienten, die Zunahme von Infektionen und die Verlängerung der Allergiesesaison spielen medizinisch eine bedeutsame Rolle. Aber auch in der Prävention und der Aufklärung der Patienten kommt den Hausärztinnen und -ärzten eine besondere Rolle zu. Direkt aus der Praxis berichtet im Live-Webinar am 13. Mai von 18 bis 19 Uhr unser Experte Dr. med. Robin Maitra.
Erweiterte Suche
Anmelden
nach oben
Tumor Biology
Erschienen in: Tumor Biology 5/2012

01.10.2012 | Research Article

Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis

verfasst von: Lin Yang, Xin Hu, Luhang Xu

Erschienen in: Tumor Biology | Ausgabe 5/2012

Einloggen, um Zugang zu erhalten

Abstract

The associations between methylenetetrahydrofolate reductase (MTHFR) polymorphism and methotrexate (MTX)-induced toxicities in patients with acute lymphoblastic leukemia (ALL) have been evaluated in various populations, with the results remained conflicting. Therefore, we conducted a meta-analysis by combining available data to derive a more precise estimation of the association. PubMed, Embase, and China National Knowledge Infrastructure were searched until 21 September 2011 to identify eligible studies. A total of 14 studies were included, with all studies investigating MTHFR C677T polymorphism while nine of them investigating MTHFR A1298C polymorphism only. Results suggested that MTHFR C677T polymorphism was associated with significantly increased risk of MTX-induced toxicity, specifically liver toxicity (TT/CT vs. CC: odds ratio (OR) = 1.70, 95 % confidence interval (CI) = 1.05–2.75), myelosuppression (TT vs. CT/CC: OR = 2.82, 95 %CI = 1.25–6.34), oral mucositis (TT/CT vs. CC: OR = 3.68, 95 %CI = 1.73–7.85), gastrointestinal toxicity (TT/CT vs. CC: OR = 2.36, 95 %CI = 1.36–4.11), and skin toxicity (T vs. C: OR = 2.26, 95 %CI = 1.07–4.74). MTHFR A1298C polymorphism was found to be associated with decreased risk of skin toxicity (CC/AC vs. AA: OR = 0.11, 95 %CI = 0.01–0.85). Genotyping of MTHFR polymorphism, C677T particularly, prior to treatment for ALL is likely to be useful with the aim of tailoring MTX therapy and thus reducing the MTX-related toxicities. However, further studies with larger data set and well-designed models are required to validate our findings.
Literatur
1.
Lopez-Lopez E, Martin-Guerrero I, Ballesteros J, Pinan MA, Garcia-Miguel P, Navajas A, Garcia-Orad A. Polymorphisms of the slco1b1 gene predict methotrexate-related toxicity in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2011;57:612–9.CrossRefPubMed
2.
Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med. 2004;350:1535–48.CrossRefPubMed
3.
Kishi S, Cheng C, French D, Pei D, Das S, Cook EH, Hijiya N, Rizzari C, Rosner GL, Frudakis T, Pui CH, Evans WE, Relling MV. Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood. 2007;109:4151–7.CrossRefPubMedPubMedCentral
4.
Tantawy AA, El-Bostany EA, Adly AA, Abou El Asrar M, El-Ghouroury EA, Abdulghaffar EE. Methylene tetrahydrofolate reductase gene polymorphism in Egyptian children with acute lymphoblastic leukemia. Blood Coagul Fibrinolysis. 2010;21:28–34.CrossRefPubMed
5.
Skibola CF, Smith MT, Kane E, Roman E, Rollinson S, Cartwright RA, Morgan G. Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. Proc Natl Acad Sci USA. 1999;96:12810–5.CrossRefPubMedPubMedCentral
6.
Narayanan S, McConnell J, Little J, Sharp L, Piyathilake CJ, Powers H, Basten G, Duthie SJ. Associations between two common variants c677t and a1298c in the methylenetetrahydrofolate reductase gene and measures of folate metabolism and DNA stability (strand breaks, misincorporated uracil, and DNA methylation status) in human lymphocytes in vivo. Cancer Epidemiol Biomarkers Prev. 2004;13:1436–43.PubMed
7.
Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–3.CrossRefPubMed
8.
van der Put NM, Gabreels F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK, van den Heuvel LP, Blom HJ. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998;62:1044–51.CrossRefPubMedPubMedCentral
9.
Toffoli G, Russo A, Innocenti F, Corona G, Tumolo S, Sartor F, Mini E, Boiocchi M. Effect of methylenetetrahydrofolate reductase 677c–>t polymorphism on toxicity and homocysteine plasma level after chronic methotrexate treatment of ovarian cancer patients. Int J Cancer. 2003;103:294–9.CrossRefPubMed
10.
Taniguchi A, Urano W, Tanaka E, Furihata S, Kamitsuji S, Inoue E, Yamanaka M, Yamanaka H, Kamatani N. Validation of the associations between single nucleotide polymorphisms or haplotypes and responses to disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a proposal for prospective pharmacogenomic study in clinical practice. Pharmacogenet Genomics. 2007;17:383–90.CrossRefPubMed
11.
Ulrich CM, Yasui Y, Storb R, Schubert MM, Wagner JL, Bigler J, Ariail KS, Keener CL, Li S, Liu H, Farin FM, Potter JD. Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase c677t polymorphism. Blood. 2001;98:231–4.CrossRefPubMed
12.
Chiusolo P, Reddiconto G, Casorelli I, Laurenti L, Sora F, Mele L, Annino L, Leone G, Sica S. Preponderance of methylenetetrahydrofolate reductase c677t homozygosity among leukemia patients intolerant to methotrexate. Ann Oncol. 2002;13:1915–8.CrossRefPubMed
13.
Ongaro A, De Mattei M, Della Porta MG, Rigolin G, Ambrosio C, Di Raimondo F, Pellati A, Masieri FF, Caruso A, Catozzi L, Gemmati D. Gene polymorphisms in folate metabolizing enzymes in adult acute lymphoblastic leukemia: effects on methotrexate-related toxicity and survival. Haematologica. 2009;94:1391–8.CrossRefPubMedPubMedCentral
14.
Karathanasis NV, Stiakaki E, Goulielmos GN, Kalmanti M. The role of the methylenetetrahydrofolate reductase 677 and 1298 polymorphisms in cretan children with acute lymphoblastic leukemia. Genet Test Mol Biomarkers. 2011;15:5–10.CrossRefPubMed
15.
Ruiz-Arguelles GJ, Coconi-Linares LN, Garces-Eisele J, Reyes-Nunez V. Methotrexate-induced mucositis in acute leukemia patients is not associated with the MTHFR 677T allele in Mexico. Hematology. 2007;12:387–91.CrossRefPubMed
16.
van Kooten Niekerk PB, Schmiegelow K, Schroeder H. Influence of methylene tetrahydrofolate reductase polymorphisms and coadministration of antimetabolites on toxicity after high dose methotrexate. Eur J Haematol. 2008;81:391–8.PubMed
17.
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMed
18.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMed
19.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the prisma statement. PLoS Med. 2009;6:e1000097.CrossRefPubMedPubMedCentral
20.
Imanishi H, Okamura N, Yagi M, Noro Y, Moriya Y, Nakamura T, Hayakawa A, Takeshima Y, Sakaeda T, Matsuo M, Okumura K. Genetic polymorphisms associated with adverse events and elimination of methotrexate in childhood acute lymphoblastic leukemia and malignant lymphoma. J Hum Genet. 2007;52:166–71.CrossRefPubMed
21.
Faganel Kotnik B, Grabnar I, Bohanec Grabar P, Dolzan V, Jazbec J. Association of genetic polymorphism in the folate metabolic pathway with methotrexate pharmacokinetics and toxicity in childhood acute lymphoblastic leukaemia and malignant lymphoma. Eur J Clin Pharmacol. 2011;67:993–1006.CrossRefPubMed
22.
Kantar M, Kosova B, Cetingul N, Gumus S, Toroslu E, Zafer N, Topcuoglu N, Aksoylar S, Cinar M, Tetik A, Eroglu Z. Methylenetetrahydrofolate reductase c677t and a1298c gene polymorphisms and therapy-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. Leuk Lymphoma. 2009;50:912–7.CrossRefPubMed
23.
Taub JW, Matherly LH, Ravindranath Y, Kaspers GJ, Rots MG, Zantwijk CH. Polymorphisms in methylenetetrahydrofolate reductase and methotrexate sensitivity in childhood acute lymphoblastic leukemia. Leukemia. 2002;16:764–5.CrossRefPubMed
24.
Krajinovic M, Lemieux-Blanchard E, Chiasson S, Primeau M, Costea I, Moghrabi A. Role of polymorphisms in MTHFR and MTHFD1 genes in the outcome of childhood acute lymphoblastic leukemia. Pharmacogenomics J. 2004;4:66–72.CrossRefPubMed
25.
Nowak-Gottl U, Wermes C, Junker R, Koch HG, Schobess R, Fleischhack G, Schwabe D, Ehrenforth S. Prospective evaluation of the thrombotic risk in children with acute lymphoblastic leukemia carrying the MTHFR TT 677 genotype, the prothrombin G20210A variant, and further prothrombotic risk factors. Blood. 1999;93:1595–9.PubMed
26.
Jazbec J, Kitanovski L, Aplenc R, Debeljak M, Dolzan V. No evidence of association of methylenetetrahydrofolate reductase polymorphism with occurrence of second neoplasms after treatment of childhood leukemia. Leuk Lymphoma. 2005;46:893–7.CrossRefPubMed
27.
Chatzidakis K, Goulas A, Athanassiadou-Piperopoulou F, Fidani L, Koliouskas D, Mirtsou V. Methylenetetrahydrofolate reductase c677t polymorphism: association with risk for childhood acute lymphoblastic leukemia and response during the initial phase of chemotherapy in Greek patients. Pediatr Blood Cancer. 2006;47:147–51.CrossRefPubMed
28.
Karas Kuzelicki N, Milek M, Jazbec J, Mlinaric-Rascan I. 5,10-Methylenetetrahydrofolate reductase (MTHFR) low activity genotypes reduce the risk of relapse-related acute lymphoblastic leukemia (ALL). Leuk Res. 2009;33:1344–8.CrossRefPubMed
29.
Krajinovic M, Robaey P, Chiasson S, Lemieux-Blanchard E, Rouillard M, Primeau M, Bournissen FG, Moghrabi A. Polymorphisms of genes controlling homocysteine levels and IQ score following the treatment for childhood ALL. Pharmacogenomics. 2005;6:293–302.CrossRefPubMed
30.
Kamdar KY, Krull KR, El-Zein RA, Brouwers P, Potter BS, Harris LL, Holm S, Dreyer Z, Scaglia F, Etzel CJ, Bondy M, Okcu MF. Folate pathway polymorphisms predict deficits in attention and processing speed after childhood leukemia therapy. Pediatr Blood Cancer. 2011;57:454–60.CrossRefPubMedPubMedCentral
31.
Salazar J, Altes A, Del Rio E, Estella J, Rives S, Tasso M, Navajas A, Molina J, Villa M, Vivanco JL, Torrent M, Baiget M, Badell I (2012) Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia. Pharmacogenomics J. doi:10.​1038/​tpj.​2011.​25
32.
El-Khodary NM, El-Haggar SM, Eid MA, Ebeid EN (2012) Study of the pharmacokinetic and pharmacogenetic contribution to the toxicity of high-dose methotrexate in children with acute lymphoblastic leukemia. Med Oncol. doi:10.​1007/​s12032-011-9997-6
33.
Costea I, Moghrabi A, Laverdiere C, Graziani A, Krajinovic M. Folate cycle gene variants and chemotherapy toxicity in pediatric patients with acute lymphoblastic leukemia. Haematologica. 2006;91:1113–6.PubMed
34.
Xu KK, Liao QC, Zhang Y, Xu J, Luo L, Wang CX, Peng XX. Influence of MTHFR C677T and RFC1 G80A gene polymorphisms on adverse reactions of high dose methotrexate chemotherapy in children with acute lymphoblastic leukemia. J Appl Clin Pediatr. 2009;24:1674–6.
35.
Xu H, Zhang YN, Kang XX. The relationship between methylenetetrahydrofolate reductase gene polymorphism and serum concentration of methotrexate in children with acute lymphoblastic leukemia. Chin J Lab Diagn. 2010;14:676–9.
36.
Li TY, Wang B, Xu KK, Xu J, Gu HJ, Liao QC, Yang L, Yan HL. Polymorphism C677T in methylenetetrahydrofolate reductase gene and its relationship to methotrexate-induced toxicities of childhood acute lymphoblastic leukemia. Acta Univ Med Nanjing (Nat Sci). 2010;30:386–9, 404.
37.
Liu SG, Li ZG, Cui L, Gao C, Li WJ, Zhao XX. Effects of methylenetetrahydrofolate reductase gene polymorphisms on toxicities during consolidation therapy in pediatric acute lymphoblastic leukemia in a Chinese population. Leuk Lymphoma. 2011;52:1030–40.CrossRefPubMed
38.
Karas-Kuzelicki N, Jazbec J, Milek M, Mlinaric-Rascan I. Heterozygosity at the TPMT gene locus, augmented by mutated MTHFR gene, predisposes to 6-MP related toxicities in childhood all patients. Leukemia. 2009;23:971–4.CrossRefPubMed
39.
Shimasaki N, Mori T, Samejima H, Sato R, Shimada H, Yahagi N, Torii C, Yoshihara H, Tanigawara Y, Takahashi T, Kosaki K. Effects of methylenetetrahydrofolate reductase and reduced folate carrier 1 polymorphisms on high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia or lymphoma. J Pediatr Hematol Oncol. 2006;28:64–8.CrossRefPubMed
40.
Aplenc R, Thompson J, Han P, La M, Zhao H, Lange B, Rebbeck T. Methylenetetrahydrofolate reductase polymorphisms and therapy response in pediatric acute lymphoblastic leukemia. Cancer Res. 2005;65:2482–7.CrossRefPubMed
41.
Kishi S, Griener J, Cheng C, Das S, Cook EH, Pei D, Hudson M, Rubnitz J, Sandlund JT, Pui CH, Relling MV. Homocysteine, pharmacogenetics, and neurotoxicity in children with leukemia. J Clin Oncol. 2003;21:3084–91.CrossRefPubMed
42.
D’Angelo V, Ramaglia M, Iannotta A, Crisci S, Indolfi P, Francese M, Affinita MC, Pecoraro G, Napolitano A, Fusco C, Oreste M, Indolfi C, Casale F. Methotrexate toxicity and efficacy during the consolidation phase in paediatric acute lymphoblastic leukaemia and MTHFR polymorphisms as pharmacogenetic determinants. Cancer Chemother Pharmacol. 2011;68(5):1339–46.CrossRefPubMed
43.
Chiusolo P, Reddiconto G, Farina G, Mannocci A, Fiorini A, Palladino M, La Torre G, Fianchi L, Sora F, Laurenti L, Leone G, Sica S. MTHFR polymorphisms’ influence on outcome and toxicity in acute lymphoblastic leukemia patients. Leuk Res. 2007;31:1669–74.CrossRefPubMed
44.
Shimasaki N, Mori T, Torii C, Sato R, Shimada H, Tanigawara Y, Kosaki K, Takahashi T. Influence of MTHFR and RFC1 polymorphisms on toxicities during maintenance chemotherapy for childhood acute lymphoblastic leukemia or lymphoma. J Pediatr Hematol Oncol. 2008;30:347–52.CrossRefPubMed
45.
Huang L, Tissing WJ, de Jonge R, van Zelst BD, Pieters R. Polymorphisms in folate-related genes: association with side effects of high-dose methotrexate in childhood acute lymphoblastic leukemia. Leukemia. 2008;22:1798–800.CrossRefPubMed
46.
Krull KR, Brouwers P, Jain N, Zhang L, Bomgaars L, Dreyer Z, Mahoney D, Bottomley S, Okcu MF. Folate pathway genetic polymorphisms are related to attention disorders in childhood leukemia survivors. J Pediatr. 2008;152:101–5.CrossRefPubMed
47.
Liu JX, Chen JP, Tan W, Lin DX. Association between MTHFR gene polymorphisms and toxicity of HDMTX chemotherapy in acute lymphocytic leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008;16:488–92.PubMed
48.
Toffoli G, Veronesi A, Boiocchi M, Crivellari D. MTHFR gene polymorphism and severe toxicity during adjuvant treatment of early breast cancer with cyclophosphamide, methotrexate, and fluorouracil (CMF). Ann Oncol: Off J Eur Soc Med Oncol/ESMO. 2000;11:373–4.CrossRef
49.
Tukova J, Chladek J, Hroch M, Nemcova D, Hoza J, Dolezalova P. 677TT genotype is associated with elevated risk of methotrexate (MTX) toxicity in juvenile idiopathic arthritis: treatment outcome, erythrocyte concentrations of MTX and folates, and MTHFR polymorphisms. J Rheumatol. 2010;37:2180–6.CrossRefPubMed
50.
Caliz R, Del Amo J, Balsa A, Blanco F, Silva L, Sanmarti R, Martinez F, Collado M, Ramirez Mdel C, Tejedor D, Artieda M, Pascual-Salcedo D, Oreiro N, Andreu J, Graell E, Simon L, Martinez A, Mulero J. The C677T polymorphism in the MTHFR gene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population. Scand J Rheumatol. 2012;41:10–4.CrossRefPubMed
51.
Wessels JA, de Vries-Bouwstra JK, Heijmans BT, Slagboom PE, Goekoop-Ruiterman YP, Allaart CF, Kerstens PJ, van Zeben D, Breedveld FC, Dijkmans BA, Huizinga TW, Guchelaar HJ. Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes. Arthritis Rheum. 2006;54:1087–95.CrossRefPubMed
52.
Fisher MC, Cronstein BN. Metaanalysis of methylenetetrahydrofolate reductase (MTHFR) polymorphisms affecting methotrexate toxicity. J Rheumatol. 2009;36:539–45.CrossRefPubMedPubMedCentral
53.
Spyridopoulou KP, Dimou NL, Hamodrakas SJ, Bagos PG. Methylene tetrahydrofolate reductase gene polymorphisms and their association with methotrexate toxicity: a meta-analysis. Pharmacogenet Genomics. 2012;22:117–33.CrossRefPubMed
54.
Toffoli G, De Mattia E. Pharmacogenetic relevance of MTHFR polymorphisms. Pharmacogenomics. 2008;9:1195–206.CrossRefPubMed
55.
Pakakasama S, Kanchanakamhaeng K, Kajanachumpol S, Udomsubpayakul U, Sirachainan N, Thithapandha A, Hongeng S. Genetic polymorphisms of folate metabolic enzymes and toxicities of high dose methotrexate in children with acute lymphoblastic leukemia. Ann Hematol. 2007;86:609–11.CrossRefPubMed
Metadaten
Titel
Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis
verfasst von
Lin Yang
Xin Hu
Luhang Xu
Publikationsdatum
01.10.2012
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 5/2012
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0395-2

Weitere Artikel der Ausgabe 5/2012

Tumor Biology 5/2012 Zur Ausgabe

Research Commentary

Emerging anticarcinogenic effects of fluoxetine besides its role in the treatment of breast carcinomas

Research Article

The p53-independent induction of apoptosis in breast cancer cells in response to proteasome inhibitor bortezomib

Research Article

RETRACTED ARTICLE: A translocator protein ligand PK11195 shows antigrowth activity in human choriocarcinoma cells

Research Article

Discriminant analysis involving serum cytokine levels and prediction of the response to therapy of patients with Hodgkin lymphoma

Research Article

Cyclin D1 G870A polymorphism and lung cancer risk: a meta-analysis

Research Article

Expression of transforming growth factor-β1 (TGF-β1) and E-cadherin in glioma

Neu im Fachgebiet Onkologie

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Erhöhte Mortalität bei postpartalem Brustkrebs

07.05.2024 Mammakarzinom Nachrichten

Auch für Trägerinnen von BRCA-Varianten gilt: Erkranken sie fünf bis zehn Jahre nach der letzten Schwangerschaft an Brustkrebs, ist das Sterberisiko besonders hoch.

Hypertherme Chemotherapie bietet Chance auf Blasenerhalt

07.05.2024 Harnblasenkarzinom Nachrichten

Eine hypertherme intravesikale Chemotherapie mit Mitomycin kann für Patienten mit hochriskantem nicht muskelinvasivem Blasenkrebs eine Alternative zur radikalen Zystektomie darstellen. Kölner Urologen berichten über ihre Erfahrungen.

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Klinik aktuell Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise