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Association of STAT-3 rs1053004 and VDR rs11574077 With FOLFIRI-Related Gastrointestinal Toxicity in Metastatic Colorectal Cancer Patients

Overview of attention for article published in Frontiers in Pharmacology, April 2018
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Title
Association of STAT-3 rs1053004 and VDR rs11574077 With FOLFIRI-Related Gastrointestinal Toxicity in Metastatic Colorectal Cancer Patients
Published in
Frontiers in Pharmacology, April 2018
DOI 10.3389/fphar.2018.00367
Pubmed ID
Authors

Elena De Mattia, Erika Cecchin, Marcella Montico, Adrien Labriet, Chantal Guillemette, Eva Dreussi, Rossana Roncato, Alessia Bignucolo, Angela Buonadonna, Mario D’Andrea, Luigi Coppola, Sara Lonardi, Eric Lévesque, Derek Jonker, Félix Couture, Giuseppe Toffoli

Abstract

Pharmacogenomics has largely been applied to the personalization of irinotecan-based treatment, focusing mainly on the study of genetic variants in adsorption, distribution, metabolism, and excretion (ADME) genes. The transcriptional control of ADME gene expression is mediated by a set of nuclear factors responding to cancer-related inflammation, which could have pharmacological implications. The aim of the present study was to uncover novel genetic predictors of neutropenia and gastrointestinal toxicity risk among 246 haplotype-tagging polymorphisms in 22 genes encoding inflammation-related cytokines and transcriptional regulators of ADME genes. The study comprised overall more than 400 metastatic colorectal cancer (mCRC) patients treated with first-line FOLFIRI, grouped in a discovery and a replication cohorts. A concordant protective effect of STAT-3 rs1053004 polymorphism against the risk of grade 3-4 gastrointestinal toxicity was observed in both the cohorts of patients (OR = 0.51, p = 0.045, q = 0.521 and OR = 0.39, p = 0.043, respectively). VDR rs11574077 polymorphism was demonstrated to affect both irinotecan biliary index (BI) and glucuronidation ratio (GR) by a pharmacokinetic analysis. This effect was consistent with an increased risk of grade 3-4 gastrointestinal toxicity in the discovery cohort (OR = 4.46, p = 0.010, q = 0.305). The association was not significant in the replication cohort (OR = 1.44, p = 0.601). These findings suggest an effect of STAT-3 and VDR polymorphisms on FOLFIRI-related gastrointestinal toxicity. If prospectively validated as predictive markers, they could be used to improve the clinical management of mCRC.

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Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Other 3 14%
Student > Bachelor 3 14%
Student > Ph. D. Student 3 14%
Professor 2 9%
Researcher 2 9%
Other 2 9%
Unknown 7 32%
Readers by discipline Count As %
Medicine and Dentistry 5 23%
Pharmacology, Toxicology and Pharmaceutical Science 3 14%
Agricultural and Biological Sciences 3 14%
Biochemistry, Genetics and Molecular Biology 3 14%
Unknown 8 36%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 April 2018.
All research outputs
#20,481,952
of 23,043,346 outputs
Outputs from Frontiers in Pharmacology
#10,260
of 16,368 outputs
Outputs of similar age
#289,255
of 327,997 outputs
Outputs of similar age from Frontiers in Pharmacology
#237
of 396 outputs
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