Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially permanent adverse effect of chemotherapeutic agents including taxanes such as paclitaxel and platinum-based compounds such as oxaliplatin and carboplatin. Previous studies have suggested that genetics may impact the risk o...
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| Format: | Article |
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MDPI AG
2021-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/5/1084 |
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| author | Araba A. Adjei Camden L. Lopez Daniel J. Schaid Jeff A. Sloan Jennifer G. Le-Rademacher Charles L. Loprinzi Aaron D. Norman Janet E. Olson Fergus J. Couch Andreas S. Beutler Celine M. Vachon Kathryn J. Ruddy |
| author_facet | Araba A. Adjei Camden L. Lopez Daniel J. Schaid Jeff A. Sloan Jennifer G. Le-Rademacher Charles L. Loprinzi Aaron D. Norman Janet E. Olson Fergus J. Couch Andreas S. Beutler Celine M. Vachon Kathryn J. Ruddy |
| author_sort | Araba A. Adjei |
| collection | DOAJ |
| description | Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially permanent adverse effect of chemotherapeutic agents including taxanes such as paclitaxel and platinum-based compounds such as oxaliplatin and carboplatin. Previous studies have suggested that genetics may impact the risk of CIPN. We conducted genome-wide association studies (GWASs) for CIPN in two independent populations who had completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-CIPN20 assessments (a CIPN-specific 20-item questionnaire which includes three scales that evaluate sensory, autonomic, and motor symptoms). The study population N08Cx included 692 participants from three clinical trials (North Central Cancer Treatment Group (NCCTG) N08C1, N08CA, and N08CB) who had been treated with paclitaxel, paclitaxel plus carboplatin, or oxaliplatin. The primary endpoint for the GWAS was the change from pre-chemotherapy CIPN20 sensory score to the worse score over the following 18 weeks. Study population The Mayo Clinic Breast Disease Registry (MCBDR) consisted of 381 Mayo Clinic Breast Disease Registry enrollees who had been treated with taxane or platinum-based chemotherapy. The primary endpoint for the GWAS assessed was the earliest CIPN20 sensory score available after the completion of chemotherapy. In multivariate model analyses, chemotherapy regimen (<i>p</i> = 3.0 × 10<sup>−8</sup>) and genetic ancestry (<i>p</i> = 0.007) were significantly associated with CIPN in the N08Cx population. Only age (<i>p</i> = 0.0004) was significantly associated with CIPN in the MCBDR population. The SNP most associated with CIPN was rs56360211 near <i>PDE6C</i> (<i>p</i> =7.92 × 10<sup>−8</sup>) in N08Cx and rs113807868 near <i>TMEM150C</i> in the MCBDR (<i>p</i> = 1.27 × 10<sup>−8</sup>). Due to a lack of replication, we cannot conclude that we identified any genetic predictors of CIPN. |
| first_indexed | 2024-03-09T05:44:45Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T05:44:45Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-039b5125f8a9487c8b50dfa5b263bd122023-12-03T12:21:30ZengMDPI AGCancers2072-66942021-03-01135108410.3390/cancers13051084Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB StudyAraba A. Adjei0Camden L. Lopez1Daniel J. Schaid2Jeff A. Sloan3Jennifer G. Le-Rademacher4Charles L. Loprinzi5Aaron D. Norman6Janet E. Olson7Fergus J. Couch8Andreas S. Beutler9Celine M. Vachon10Kathryn J. Ruddy11Department of Oncology, Mayo Clinic, Rochester, MN 55905, USADepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USADepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USADepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USADepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USADepartment of Oncology, Mayo Clinic, Rochester, MN 55905, USADepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USADepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USADepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USADepartment of Oncology, Mayo Clinic, Rochester, MN 55905, USADepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USADepartment of Oncology, Mayo Clinic, Rochester, MN 55905, USAChemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially permanent adverse effect of chemotherapeutic agents including taxanes such as paclitaxel and platinum-based compounds such as oxaliplatin and carboplatin. Previous studies have suggested that genetics may impact the risk of CIPN. We conducted genome-wide association studies (GWASs) for CIPN in two independent populations who had completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-CIPN20 assessments (a CIPN-specific 20-item questionnaire which includes three scales that evaluate sensory, autonomic, and motor symptoms). The study population N08Cx included 692 participants from three clinical trials (North Central Cancer Treatment Group (NCCTG) N08C1, N08CA, and N08CB) who had been treated with paclitaxel, paclitaxel plus carboplatin, or oxaliplatin. The primary endpoint for the GWAS was the change from pre-chemotherapy CIPN20 sensory score to the worse score over the following 18 weeks. Study population The Mayo Clinic Breast Disease Registry (MCBDR) consisted of 381 Mayo Clinic Breast Disease Registry enrollees who had been treated with taxane or platinum-based chemotherapy. The primary endpoint for the GWAS assessed was the earliest CIPN20 sensory score available after the completion of chemotherapy. In multivariate model analyses, chemotherapy regimen (<i>p</i> = 3.0 × 10<sup>−8</sup>) and genetic ancestry (<i>p</i> = 0.007) were significantly associated with CIPN in the N08Cx population. Only age (<i>p</i> = 0.0004) was significantly associated with CIPN in the MCBDR population. The SNP most associated with CIPN was rs56360211 near <i>PDE6C</i> (<i>p</i> =7.92 × 10<sup>−8</sup>) in N08Cx and rs113807868 near <i>TMEM150C</i> in the MCBDR (<i>p</i> = 1.27 × 10<sup>−8</sup>). Due to a lack of replication, we cannot conclude that we identified any genetic predictors of CIPN.https://www.mdpi.com/2072-6694/13/5/1084chemotherapy-induced peripheral neuropathygenome-wide associated studytoxicity |
| spellingShingle | Araba A. Adjei Camden L. Lopez Daniel J. Schaid Jeff A. Sloan Jennifer G. Le-Rademacher Charles L. Loprinzi Aaron D. Norman Janet E. Olson Fergus J. Couch Andreas S. Beutler Celine M. Vachon Kathryn J. Ruddy Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study Cancers chemotherapy-induced peripheral neuropathy genome-wide associated study toxicity |
| title | Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study |
| title_full | Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study |
| title_fullStr | Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study |
| title_full_unstemmed | Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study |
| title_short | Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study |
| title_sort | genetic predictors of chemotherapy induced peripheral neuropathy from paclitaxel carboplatin and oxaliplatin ncctg alliance n08c1 n08ca and n08cb study |
| topic | chemotherapy-induced peripheral neuropathy genome-wide associated study toxicity |
| url | https://www.mdpi.com/2072-6694/13/5/1084 |
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