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Chemotherapy-induced peripheral neuropathy : Evidence from genome-wide association studies and replication within multiple myeloma patients

Mahmoudpour, Seyed Hamidreza LU ; Bandapalli, Obul Reddy; da Silva Filho, Miguel Inácio LU ; Campo, Chiara; Hemminki, Kari LU ; Goldschmidt, Hartmut; Merz, Maximilian and Försti, Asta LU (2018) In BMC Cancer 18(1).
Abstract

Background: Based on the possible shared mechanisms of chemotherapy-induced peripheral neuropathy (CIPN) for different drugs, we aimed to aggregate results of all previously published genome-wide association studies (GWAS) on CIPN, and to replicate them within a cohort of multiple myeloma (MM) patients. Methods: Following a systematic literature search, data for CIPN associated single nucleotide polymorphisms (SNPs) with P-values<10-5 were extracted; these associations were investigated within a cohort of 983 German MM patients treated with bortezomib, thalidomide or vincristine. Cases were subjects that developed CIPN grade 2-4 while controls developed no or sub-clinical CIPN. Logistic regression with additive model was... (More)

Background: Based on the possible shared mechanisms of chemotherapy-induced peripheral neuropathy (CIPN) for different drugs, we aimed to aggregate results of all previously published genome-wide association studies (GWAS) on CIPN, and to replicate them within a cohort of multiple myeloma (MM) patients. Methods: Following a systematic literature search, data for CIPN associated single nucleotide polymorphisms (SNPs) with P-values<10-5 were extracted; these associations were investigated within a cohort of 983 German MM patients treated with bortezomib, thalidomide or vincristine. Cases were subjects that developed CIPN grade 2-4 while controls developed no or sub-clinical CIPN. Logistic regression with additive model was used. Results: In total, 9 GWASs were identified from the literature on CIPN caused by different drugs (4 paclitaxel, 2 bortezomib, 1 vincristine, 1 docetaxel, and 1 oxaliplatin). Data were extracted for 526 SNPs in 109 loci. One hundred fourty-eight patients in our study population were CIPN cases (102/646 bortezomib, 17/63 thalidomide and 29/274 vincristine). In total, 13 SNPs in 9 loci were replicated in our population (p-value< 0.05). The four smallest P-values relevant to the nerve function were 0.0006 for rs8014839 (close to the FBXO33 gene), 0.004 for rs4618330 (close to the INTU gene), 0.006 for rs1903216 (close to the BCL6 gene) and 0.03 for rs4687753 (close to the IL17RB gene). Conclusions: Replicated SNPs provide clues of the molecular mechanism of CIPN and can be strong candidates for further research aiming to predict the risk of CIPN in clinical practice, particularly rs8014839, rs4618330, rs1903216, and rs4687753, which showed relevance to the function of nervous system.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adverse drug reaction, Chemotherapy, GWAS, Multiple myeloma, Neuropathy
in
BMC Cancer
volume
18
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85051722404
ISSN
1471-2407
DOI
10.1186/s12885-018-4728-4
language
English
LU publication?
yes
id
6fece220-7cc6-4556-91cd-9e7bd13850d8
date added to LUP
2018-09-10 09:42:07
date last changed
2019-11-17 04:49:54
@article{6fece220-7cc6-4556-91cd-9e7bd13850d8,
  abstract     = {<p>Background: Based on the possible shared mechanisms of chemotherapy-induced peripheral neuropathy (CIPN) for different drugs, we aimed to aggregate results of all previously published genome-wide association studies (GWAS) on CIPN, and to replicate them within a cohort of multiple myeloma (MM) patients. Methods: Following a systematic literature search, data for CIPN associated single nucleotide polymorphisms (SNPs) with P-values&lt;10<sup>-5</sup> were extracted; these associations were investigated within a cohort of 983 German MM patients treated with bortezomib, thalidomide or vincristine. Cases were subjects that developed CIPN grade 2-4 while controls developed no or sub-clinical CIPN. Logistic regression with additive model was used. Results: In total, 9 GWASs were identified from the literature on CIPN caused by different drugs (4 paclitaxel, 2 bortezomib, 1 vincristine, 1 docetaxel, and 1 oxaliplatin). Data were extracted for 526 SNPs in 109 loci. One hundred fourty-eight patients in our study population were CIPN cases (102/646 bortezomib, 17/63 thalidomide and 29/274 vincristine). In total, 13 SNPs in 9 loci were replicated in our population (p-value&lt; 0.05). The four smallest P-values relevant to the nerve function were 0.0006 for rs8014839 (close to the FBXO33 gene), 0.004 for rs4618330 (close to the INTU gene), 0.006 for rs1903216 (close to the BCL6 gene) and 0.03 for rs4687753 (close to the IL17RB gene). Conclusions: Replicated SNPs provide clues of the molecular mechanism of CIPN and can be strong candidates for further research aiming to predict the risk of CIPN in clinical practice, particularly rs8014839, rs4618330, rs1903216, and rs4687753, which showed relevance to the function of nervous system.</p>},
  articleno    = {820},
  author       = {Mahmoudpour, Seyed Hamidreza and Bandapalli, Obul Reddy and da Silva Filho, Miguel Inácio and Campo, Chiara and Hemminki, Kari and Goldschmidt, Hartmut and Merz, Maximilian and Försti, Asta},
  issn         = {1471-2407},
  keyword      = {Adverse drug reaction,Chemotherapy,GWAS,Multiple myeloma,Neuropathy},
  language     = {eng},
  month        = {08},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {BMC Cancer},
  title        = {Chemotherapy-induced peripheral neuropathy : Evidence from genome-wide association studies and replication within multiple myeloma patients},
  url          = {http://dx.doi.org/10.1186/s12885-018-4728-4},
  volume       = {18},
  year         = {2018},
}