Pharmacogenetic analysis of irreversible severe cisplatin‐induced nephropathy: a case report of a 27‐year‐old woman

Abstract

In this report we describe a young patient diagnosed with bulky FIGO stage IIIb squamous cell cervix carcinoma with severe and irreversible nephropathy after three weekly low-doses of cisplatin. Besides several known risk factors such as hypomagnesemia and hypoalbuminemia, the patient also proved to be homozygously polymorphic for two polymorphisms within the COMT gene (c.615 + 310C>T and c.616-367C>T). As COMT polymorphism has been associated with cisplatin-induced ototoxicity, its effect on nephrotoxicity of cisplatin should be the subject of further investigation.

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

“…Single nucleotide polymorphisms (SNPs) in five candidate genes, of which two are SNPs in COMT, were genotyped in a young woman who developed severe irreversible cisplatin-induced nephropathy. Both COMT polymorphisms were already known to be associated with cisplatin induced ototoxicity [4,5] and were homozygous polymorphic in this patient (c.615 + 310C>T (rs4646316) and c.616-367C>T (rs9332377)) [3]. As COMT is an enzyme that inactivates catecholamines by transferring a methyl group of S-adenosyl methionine (SAM) into a catecholamine neurotransmitter (such as dopamine, epinephrine, and norepinephrine), the authors hypothesized that the mechanism of cisplatin-induced nephrotoxicity could be mediated by increased SAM concentrations.…”

“…In a recently published case report, the potential role of catechol-O-methyltransferase (COMT) on cisplatin-induced nephrotoxicity was suggested [3]. Single nucleotide polymorphisms (SNPs) in five candidate genes, of which two are SNPs in COMT, were genotyped in a young woman who developed severe irreversible cisplatin-induced nephropathy.…”