| Autor: |
Kratz, C P, Franke, L, Peters, H, Kohlschmidt, N, Kazmierczak, B, Finckh, U, Bier, A, Eichhorn, B, Blank, C, Kraus, C, Kohlhase, J, Pauli, S, Wildhardt, G, Kutsche, K, Auber, B, Christmann, A, Bachmann, N, Mitter, D, Cremer, F W, Mayer, K |
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| Zdroj: |
British Journal of Cancer; 4/14/2015, Vol. 112 Issue 8, p1392-1397, 6p, 3 Charts |
| Abstrakt: |
Background:Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These 'RASopathies' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown.Methods:We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry.Results:We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR)=10.5, 95% confidence interval=5.4-18.3). The specific cancers included juvenile myelomonocytic leukaemia=4; brain tumour=3; acute lymphoblastic leukaemia=2; rhabdomyosarcoma=2; and neuroblastoma=1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4.Conclusions:These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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