Large-scale prospective genome-wide association study of oxaliplatin in stage II/III colon cancer and neuropathy

被引：6
|
作者：
Kanai, M. [1 ]
Kawaguchi, T. [2 ]
Kotaka, M. [3 ]
Manaka, D. [4 ]
Hasegawa, J. [5 ]
Takagane, A. [6 ]
Munemoto, Y. [7 ]
Kato, T. [8 ]
Eto, T. [9 ]
Touyama, T. [10 ]
Matsui, T. [11 ]
Shinozaki, K. [12 ]
Matsumoto, S. [13 ]
Mizushima, T. [14 ]
Mori, M. [15 ]
Sakamoto, J. [16 ,17 ]
Ohtsu, A. [18 ]
Yoshino, T. [18 ]
Saji, S. [16 ]
Matsuda, F. [2 ]
机构：
[1] Kyoto Univ, Grad Sch Med, Dept Therapeut Oncol, Kyoto, Japan
[2] Kyoto Univ, Ctr Genom Med, Grad Sch Med, Kyoto, Japan
[3] Sano Hosp, Gastrointestinal Canc Ctr, Kobe, Hyogo, Japan
[4] Kyoto Katsura Hosp, Gastrointestinal Ctr, Dept Surg, Kyoto, Japan
[5] Osaka Rosai Hosp, Dept Surg, Osaka, Japan
[6] Hakodate Goryoukaku Hosp, Dept Surg, Hakodate, Hokkaido, Japan
[7] Fukui Ken Saiseikai Hosp, Dept Surg, Fukui, Japan
[8] Kansai Rosai Hosp, Dept Surg, Amagasaki, Hyogo, Japan
[9] Tsuchiura Kyodo Gen Hosp, Dept Gastroenterol, Ibaraki, Japan
[10] Nakagami Hosp, Dept Surg, Okinawa City, Okinawa, Japan
[11] Aichi Hosp, Dept Gastroenterol Surg, Aichi Canc Ctr, Nagoya, Aichi, Japan
[12] Hiroshima Prefectural Hosp, Div Clin Oncol, Hiroshima, Japan
[13] Kyoto Univ, Grad Sch Med, Dept Real World Data Res & Dev, Kyoto, Japan
[14] Osaka Univ, Dept Gastroenterol Surg, Grad Sch Med, Osaka, Japan
[15] Kyushu Univ, Dept Surg & Sci, Fukuoka, Japan
[16] Japanese Fdn Multidisciplinary Treatment Canc, Tokyo, Japan
[17] Tokai Cent Hosp, Kakamigahara, Japan
[18] Natl Canc Ctr Hosp East, Dept Gastroenterol & Gastrointestinal Oncol, Chiba, Japan
来源：
ANNALS OF ONCOLOGY | 2021年 / 32卷 / 11期
关键词：
oxaliplatin; peripheral sensory neuropathy; genome-wide association study; pharmacogenomics; colon cancer; INDUCED PERIPHERAL NEUROPATHY; PHASE-III TRIAL; PHARMACOGENETIC PREDICTORS; ADJUVANT CHEMOTHERAPY; CUMULATIVE NEUROPATHY; POLYMORPHISMS; NEUROTOXICITY; ILE(105)VAL;
D O I：
10.1016/j.annonc.2021.08.1745
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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 I.OHP-based adjuvant chemotherapy (mFOLFOX6/CAPDX) 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 x 10(-8)) in either GWAS comparison of worst grade PSN, extreme PSN phenotypes, or time to recovery from PSN. An association study focusing on AR or time to disease recurrence also failed to reveal any significant SNPs. Conclusion: Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.
引用
收藏
页码：1434 / 1441
页数：8
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