Large-scale prospective genome-wide association study of oxaliplatin in stage II/III colon cancer and neuropathy.
Antineoplastic Combined Chemotherapy Protocols
Chemotherapy, Adjuvant
Clinical Trials, Phase II as Topic
Clinical Trials, Phase III as Topic
Colonic Neoplasms
/ drug therapy
Fluorouracil
/ therapeutic use
Genome-Wide Association Study
Humans
Neoplasm Recurrence, Local
Oxaliplatin
/ adverse effects
Prospective Studies
colon cancer
genome-wide association study
oxaliplatin
peripheral sensory neuropathy
pharmacogenomics
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
06
04
2021
revised:
20
07
2021
accepted:
04
08
2021
pubmed:
16
8
2021
medline:
29
10
2021
entrez:
15
8
2021
Statut:
ppublish
Résumé
The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach. A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored. No SNPs exceeded the genome-wide significance (P < 5.0 × 10 Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.
Sections du résumé
BACKGROUND
The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach.
PATIENTS AND METHODS
A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored.
RESULTS
No SNPs exceeded the genome-wide significance (P < 5.0 × 10
CONCLUSION
Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.
Identifiants
pubmed: 34391895
pii: S0923-7534(21)03974-0
doi: 10.1016/j.annonc.2021.08.1745
pii:
doi:
Substances chimiques
Oxaliplatin
04ZR38536J
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1434-1441Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure MKa reports honoraria from Chugai Pharmaceutical Co., Ltd. MKo reports honoraria from Chugai Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd., and Takeda Pharmaceutical Company Limited. JH reports speaker bureau from Chugai Pharmaceutical Co., Ltd. and Yakult Honsha Co., Ltd. TK reports honoraria from Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Taiho Pharmaceutical Co., Ltd, ONO Pharmaceutical Co., Ltd. and research grant from Chugai Pharmaceutical Co., Ltd. and Takeda Pharmaceutical Company Limited. SM reports research grant from NTT Ltd., H.U. Group, and Canon Medical Systems. TM reports research grant from Takeda Pharmaceutical Company Limited, Shire Japan, Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd., Eli Lilly Japan, ONO Pharmaceutical Co., Ltd., Sanofi, Mitsubishi Tanabe, Kaken, Japan Blood Products Organization, Tsumura, Astellas, Pfizer Japan, Daiichi Sankyo, Merck Biopharma, and MSD. AO reports honoraria from BMS, ONO Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Chugai Pharmaceutical Co., Ltd. and research grant from BMS. TY reports honoraria from Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Bayer Yakuhin, Ltd., Merck Biopharma Co., Ltd., and Takeda Pharmaceutical Company Limited and research grant from MSD K.K., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., Parexel International Inc., Sanofi K.K. Taiho Pharmaceutical Co., Ltd., Amgen K.K., and GlaxoSmithKline K.K. FM reports research grant from Yakult Honsha Co., Ltd. All other authors have declared no conflicts of interest.