Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array.
Por:
García-Sanz R, Corchete LA, Alcoceba M, Chillon MC, Jiménez C, Prieto I, García-Álvarez M, Puig N, Rapado I, Barrio S, Oriol A, Blanchard MJ, de la Rubia J, Martínez R, Lahuerta JJ, González Díaz M, Mateos MV, San Miguel JF, Martínez-López J, Sarasquete ME and GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en
Publicada:
1 dic 2017
Ahead of Print:
8 sep 2016
Resumen:
Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment.
Filiaciones:
García-Sanz R:
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain
Corchete LA:
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain
Alcoceba M:
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain
Chillon MC:
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain
Jiménez C:
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain
Prieto I:
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain
García-Álvarez M:
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain
Puig N:
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain
Rapado I:
Hospital 12 de Octubre, Madrid, Spain
Barrio S:
Hospital 12 de Octubre, Madrid, Spain
Oriol A:
Hospital Germans Trias i Pujol, Badalona, Spain
Blanchard MJ:
Hospital Universitario Ramón y Cajal de Madrid, Madrid, Spain
:
Hospital Dr Peset de Valencia, Valencia, Spain
Martínez R:
Hospital Clínico de San Carlos de Madrid, Madrid, Spain
Lahuerta JJ:
Hospital 12 de Octubre, Madrid, Spain
González Díaz M:
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
Mateos MV:
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain
San Miguel JF:
Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), IDISNA, Pamplona, Spain
Martínez-López J:
Hospital 12 de Octubre, Madrid, Spain
Sarasquete ME:
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain
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