Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array.
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.
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
Ramón
R
García-Sanz
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
Luis Antonio
LA
Corchete
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
Miguel
M
Alcoceba
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
María Carmen
MC
Chillon
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
Cristina
C
Jiménez
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
Isabel
I
Prieto
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
María
M
García-Álvarez
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
Noemi
N
Puig
Hospital 12 de Octubre, Madrid, Spain.
Immaculada
I
Rapado
Hospital 12 de Octubre, Madrid, Spain.
Santiago
S
Barrio
Hospital Germans Trias i Pujol, Badalona, Spain.
Albert
A
Oriol
Hospital Universitario Ramón y Cajal de Madrid, Madrid, Spain.
María Jesús
MJ
Blanchard
Hospital Dr Peset de Valencia, Valencia, Spain.
Javier
J
de la Rubia
Hospital Clínico de San Carlos de Madrid, Madrid, Spain.
Rafael
R
Martínez
Hospital 12 de Octubre, Madrid, Spain.
Juan José
JJ
Lahuerta
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
Marcos
M
González Díaz
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
María Victoria
MV
Mateos
Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), IDISNA, Pamplona, Spain.
Jesús Fernando
JF
San Miguel
Hospital 12 de Octubre, Madrid, Spain.
Joaquín
J
Martínez-López
Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain.
María Eugenia
ME
Sarasquete
D000069286:Bortezomib / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000209:etiology; D020641:Polymorphism, Single Nucleotide; D013792:Thalidomide / Q000627:therapeutic use*
D013792:Thalidomide; D000069286:Bortezomib
bortezomib-induced peripheral neuropathy; genome-wide association studies; multiple myeloma; thalidomide-induced peripheral neuropathy