Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array
Por:
Garcia-Sanz, R, Corchete, LA, Alcoceba, M, Chillon, MC, Jimenez, C, Prieto, I, Garcia-Alvarez, M, Puig, N, Rapado, I, Barrio, S, Oriol, A, Blanchard, MJ, de la Rubia, J, Martinez, R, Lahuerta, JJ, Diaz, MG, Mateos, MV, San Miguel, JF, Martinez-Lopez, J and Sarasquete, ME
Publicada:
1 dic 2017
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 can led 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 (GEM05MA565, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101.1ocated 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:
Garcia-Sanz, R:
Hosp Univ Salamanca IBSAL, IBMCC CSIC, Salamanca, Spain
Corchete, LA:
Hosp Univ Salamanca IBSAL, IBMCC CSIC, Salamanca, Spain
Alcoceba, M:
Hosp Univ Salamanca IBSAL, IBMCC CSIC, Salamanca, Spain
Chillon, MC:
Hosp Univ Salamanca IBSAL, IBMCC CSIC, Salamanca, Spain
Jimenez, C:
Hosp Univ Salamanca IBSAL, IBMCC CSIC, Salamanca, Spain
Prieto, I:
Hosp Univ Salamanca IBSAL, IBMCC CSIC, Salamanca, Spain
Garcia-Alvarez, M:
Hosp Univ Salamanca IBSAL, IBMCC CSIC, Salamanca, Spain
Puig, N:
Hosp Univ Salamanca IBSAL, IBMCC CSIC, Salamanca, Spain
Rapado, I:
Hosp 12 Octubre, Madrid, Spain
Barrio, S:
Hosp 12 Octubre, Madrid, Spain
:
Hosp Badalona Germans Trias & Pujol, Badalona, Spain
Blanchard, MJ:
Hosp Univ Ramon y Cajal Madrid, Madrid, Spain
de la Rubia, J:
Hosp Dr Peset de Valencia, Valencia, Spain
Martinez, R:
Hosp Clin San Carlos Madrid, Madrid, Spain
Lahuerta, JJ:
Hosp 12 Octubre, Madrid, Spain
Diaz, MG:
Hosp Univ Salamanca IBSAL, IBMCC CSIC, Salamanca, Spain
Mateos, MV:
Hosp Univ Salamanca IBSAL, IBMCC CSIC, Salamanca, Spain
San Miguel, JF:
IDISNA, CIMA, Clin Univ Navarra, Pamplona, Spain
Martinez-Lopez, J:
Hosp 12 Octubre, Madrid, Spain
Sarasquete, ME:
Hosp Univ Salamanca IBSAL, IBMCC CSIC, Salamanca, Spain
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