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Influence of Genetic Variation in COMT on Cisplatin-Induced Nephrotoxicity in Cancer Patients.

Abstract：

:Cisplatin is a chemotherapeutic agent widely used for multiple indications. Unfortunately, in a substantial set of patients treated with cisplatin, dose-limiting acute kidney injury (AKI) occurs. Here, we assessed the association of 3 catechol-O-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) with increased cisplatin-induced nephrotoxicity. In total, 551 patients were genotyped for the 1947 G>A (Val158Met, rs4680), c.615 + 310 C>T (rs4646316), and c.616 - 367 C>T (rs9332377) polymorphisms. Associations between these variants and AKI grade ≥3 were studied. The presence of a homozygous variant of c.616-367C>T was associated with a decreased occurrence of AKI grade 3 toxicity (p = 0.014, odds ratio (OR) 0.201, 95% confidence interval (CI) (0.047-0.861)). However, we could not exclude the role of dehydration as a potential cause of AKI in 25 of the 27 patients with AKI grade 3, which potentially affected the results substantially. As a result of the low incidence of AKI grade 3 in this dataset, the lack of patients with a COMT variant, and the high number of patients with dehydration, the association between COMT variants and AKI does not seem clinically relevant.

journal_name

Genes (Basel)

journal_title

Genes

authors

Agema BC,Koolen SLW,With M,Doorn NV,Heersche N,Hoop EO,Visser S,Aerts JGJV,Bins S,Schaik RHNV,Mathijssen RHJ

doi

10.3390/genes11040358

subject

Has Abstract

pub_date

2020-03-27 00:00:00

issue

4

issn

2073-4425

pii

genes11040358

journal_volume

11

pub_type

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