Genome-wide association studies of toxicity to oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab in 1800 patients with advanced colorectal cancer.
Adenocarcinoma
/ drug therapy
Aged
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Capecitabine
/ administration & dosage
Cetuximab
/ administration & dosage
Colorectal Neoplasms
/ drug therapy
Diarrhea
/ chemically induced
Drug-Related Side Effects and Adverse Reactions
/ etiology
Female
Fluorouracil
/ administration & dosage
Genome-Wide Association Study
/ methods
Genotype
Humans
Male
Middle Aged
Oxaliplatin
/ administration & dosage
Polymorphism, Single Nucleotide
Randomized Controlled Trials as Topic
Ribosomal Proteins
/ genetics
Serine-Arginine Splicing Factors
/ genetics
Vomiting
/ chemically induced
GWAS
chemotherapy
colorectal cancer
toxicity
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
revised:
12
05
2021
received:
11
03
2021
accepted:
08
06
2021
pubmed:
17
7
2021
medline:
23
11
2021
entrez:
16
7
2021
Statut:
ppublish
Résumé
Chemotherapies administered at normal therapeutic dosages can cause significant side-effects and may result in early treatment discontinuation. Inter-individual variation in toxicity highlights the need for biomarkers to personalise treatment. We sought to identify such biomarkers by conducting 40 genome-wide association studies, together with gene and gene set analyses, for any toxicity and 10 individual toxicities in 1800 patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidine chemotherapy ± cetuximab from the MRC COIN and COIN-B trials (385 patients received FOLFOX, 360 FOLFOX + cetuximab, 707 XELOX and 348 XELOX + cetuximab). Single nucleotide polymorphisms (SNPs), genes and gene sets that reached genome-wide or suggestive significance were validated in independent patient groups. We found that MROH5 was significantly associated with neutropenia in MAGMA gene analyses in patients treated with XELOX (P = 6.6 × 10
Substances chimiques
Ribosomal Proteins
0
SCAF4 protein, human
0
ribosomal protein L17
0
Oxaliplatin
04ZR38536J
Serine-Arginine Splicing Factors
170974-22-8
Capecitabine
6804DJ8Z9U
Cetuximab
PQX0D8J21J
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1713-1722Subventions
Organisme : Medical Research Council
ID : MR/T033371/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801418
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/20
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T04604X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/25
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P005748/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C1298/A8362
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00004/01
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Références
Schmoll HJ, Van Cutsem E, Stein A, et al. Esmo consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol. 2012;23:2479-2516.
Stein A, Arnold D. Oxaliplatin: a review of approved uses. Expert Opin Pharmacother. 2012;13:125-137.
Ducreux M, Bennouna J, Hebbar M, et al. Efficacy and safety findings from a randomized phase III study of capecitabine (X) + oxaliplatin (O) (XELOX) vs. infusional 5- FU/LV + O (FOLFOX-6) for metastatic colorectal cancer (MCRC). J Clin Oncol. 2007;25:4029-4029.
Guo Y, Xiong BH, Zhang T, Cheng Y, Ma L. XELOX vs. FOLFOX in metastatic colorectal cancer: an updated meta-analysis. Cancer Invest. 2016;34:94-104.
Petrelli F, Borgonovo K, Barni S. The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials. Target Oncol. 2013;8:173-181.
Andreyev HJN, Davidson SE, Gillespie C, Allum WH, Swarbrick E. Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer. Gut. 2012;61:179-192.
Blumenthal GM, Gong Y, Kehl K, et al. Analysis of time-to-treatment discontinuation of targeted therapy, immunotherapy, and chemotherapy in clinical trials of patients with non-small-cell lung cancer. Ann Oncol. 2019;30:830-838.
Koedoot CG, De Haan RJ, Stiggelbout AM, et al. Palliative chemotherapy or best supportive care? A prospective study explaining patients' treatment preference and choice. Br J Cancer. 2003;89:2219-2226.
Huitema ADR, Spaander M, Mathôt RAA, et al. Relationship between exposure and toxicity in high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin. Ann Oncol. 2002;13:374-384.
Braun MS, Seymour MT. Balancing the efficacy and toxicity of chemotherapy in colorectal cancer. Ther Adv Med Oncol. 2011;3:43-52.
Schwab M, Zanger UM, Marx C, et al. Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU toxicity study group. J Clin Oncol. 2008;26:2131-2138.
Henricks LM, Lunenburg CATC, de Man FM, et al. DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol. 2018;19:1459-1467.
Gonzalez FJ, Fernandez-Salguaro P. Diagnostic analysis, clinical importance and molecular basis of dihydropyrimidine dehydrogenase deficiency. Trends Pharmacol Sci. 1995;16:325-327.
Wei X, McLeod HL, McMurrough J, Gonzalez FJ, Fernandez-Salguero P. Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. J Clin Invest. 1996;98:610-615.
Madi A, Fisher D, Maughan TS, et al. Pharmacogenetic analyses of 2183 patients with advanced colorectal cancer; potential role for common dihydropyrimidine dehydrogenase variants in toxicity to chemotherapy. Eur J Cancer. 2018;102:31-39.
Maughan TS, Adams RA, Smith CG, et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet. 2011;377:2103-2114.
Adams RA, Meade AM, Seymour MT, et al. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol. 2011;12:642-653.
Wasan H, Meade AM, Adams R, et al. Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial. Lancet Oncol. 2014;15:631-639.
Moore CM, Jacobson SA, Fingerlin TE. Power and sample size calculations for genetic association studies in the presence of genetic model misspecification. Hum Hered. 2019;84:256-271. https://doi.org/10.1159/000508558
Al-Tassan NA, Whiffin N, Hosking FJ, et al. A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer. Sci Rep. 2015;5:10442.
Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559-575.
Turner SD. qqman: an R package for visualizing GWAS results using Q-Q and manhattan plots. J Open Source Softw. 2018;3:731.
de Leeuw CA, Mooij JM, Heskes T, Posthuma D. MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput Biol. 2015;11:e1004219.
Kerr RS, Love S, Segelov E, et al. Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial. Lancet Oncol. 2016;17:1543-1557.
Kichaev G, Yang W-Y, Lindstrom S, et al. Integrating functional data to prioritize causal variants in statistical fine-mapping studies. PLoS Genet. 2014;10:e1004722.
Fernandez-Rozadilla C, Cazier JB, Moreno V, et al. Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration. Pharmacogenomics J. 2013;13:209-217.
Tang X, Woodward T, Amar S. A PTP4A3 peptide PIMAP39 modulates TNF-alpha levels and endotoxic shock. J Innate Immun. 2009;2:43-55.
Zimmerman MW, Homanics GE, Lazo JS. Targeted deletion of the metastasis-associated phosphatase Ptp4a3 (PRL-3) suppresses murine colon cancer. PLoS One. 2013;8:e58300.
Saha S, Bardelli A, Buckhaults P, et al. A phosphatase associated with metastasis of colorectal cancer. Science. 2001;294:1343-1346.
Csoboz B, Gombos I, Tatrai E, et al. Chemotherapy induced PRL3 expression promotes cancer growth via plasma membrane remodeling and specific alterations of caveolae-associated signaling. Cell Commun Signal. 2018;16:51.
den Hollander P, Rawls K, Tsimelzon A, et al. Phosphatase PTP4A3 promotes triple-negative breast cancer growth and predicts poor patient survival. Cancer Res. 2016;76:1942-1953.
Kim KH, Shcheynikov N, Wang Y, Muallem S. SLC26A7 is a Cl- channel regulated by intracellular pH. J Biol Chem. 2005;280:6463-6470.
Fujiwara Y, Chayahara N, Mukohara T, et al. Hypothyroidism in patients with colorectal carcinoma treated with fluoropyrimidines. Oncol Rep. 2013;30:1802-1806.
Andreyev HJN, Lalji A, Mohammed K, et al. The FOCCUS study: a prospective evaluation of the frequency, severity and treatable causes of gastrointestinal symptoms during and after chemotherapy. Support Care Cancer. 2021;29(3):1443-1453.
Hartmann PA-CK. Thyroid disorders in the oncology patient. J Adv Pract Oncol. 2015;6:99.
Xu J, Song P, Nakamura S, et al. Deletion of the chloride transporter Slc26a7 causes distal renal tubular acidosis and impairs gastric acid secretion. J Biol Chem. 2009;284:29470-29479.
Petrovic S, Ju X, Barone S, et al. Identification of a basolateral Cl−/HCO 3 − exchanger specific to gastric parietal cells. Am J Physiol Liver Physiol. 2003;284:G1093-G1103.
Sweet C, Sharma A, Lipscomb G. Recurrent nausea, vomiting and abdominal pain due to hypothyroidism. BMJ Case Rep. 2010;2010:bcr1120092461.
Raufman JP, Collins SM, Pandol SJ, et al. Reliability of symptoms in assessing control of gastric acid secretion in patients with Zollinger-Ellison syndrome. Gastroenterology. 1983;84:108-113.
Hsu HC, Lapke N, Chen SJ, et al. PTPRT and PTPRD deleterious mutations and deletion predict bevacizumab resistance in metastatic colorectal cancer patients. Cancers (Basel). 2018;10:314.
Takada K, Zhu D, Bird GH, et al. Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling. Sci Transl Med. 2012;4:148ra117.
Yasuno H, Kurasawa M, Yanagisawa M, Sato Y, Harada N, Mori K. Predictive markers of capecitabine sensitivity identified from the expression profile of pyrimidine nucleoside-metabolizing enzymes. Oncol Rep. 2013;29:451-458.
Fredrikson M, Hursti TJ, Steineck G, Fürst CJ, Börjesson S, Peterson C. Delayed chemotherapy-induced nausea is augmented by high levels of endogenous noradrenaline. Br J Cancer. 1994;70:642-645.