Genetic Variations and Cisplatin Nephrotoxicity: A Systematic Review

Area of Science:

• Pharmacogenomics
• Nephrology
• Oncology

Background:

• Cisplatin chemotherapy can cause significant nephrotoxicity (kidney damage), affecting 20-70% of patients.
• Pharmacogenomics aims to identify genetic markers for predicting adverse drug reactions and treatment efficacy.
• While genetic variations are implicated in cisplatin nephrotoxicity, a comprehensive review is needed.

Purpose of the Study:

• To systematically review and synthesize evidence on genetic variations associated with cisplatin-induced nephrotoxicity.
• To identify specific genes and single nucleotide polymorphisms (SNPs) consistently linked to this adverse effect.

Main Methods:

• A systematic literature review was conducted using PubMed, Embase, and Web of Science.
• Included studies involved cisplatin-based chemotherapy, genotyping data, and nephrotoxicity outcomes.
• Study quality was assessed using the STrengthening the REporting of Genetic Association Studies (STREGA) checklist.

Main Results:

• Twenty-eight eligible candidate gene studies were included, analyzing over 300 SNPs across 135 genes.
• Twenty-nine SNPs in 14 genes showed significant associations with cisplatin nephrotoxicity.
• Notably, variations in SLC22A2 (rs316019), ERCC1 (rs11615, rs3212986), and ERCC2 (rs13181) were consistently linked to nephrotoxicity risk.

Conclusions:

• Three genes (SLC22A2, ERCC1, ERCC2) demonstrate consistent associations with cisplatin-induced nephrotoxicity.
• Further research is required to elucidate the biological mechanisms and clinical utility of these genetic markers for treatment modification.