Systematic Reviews/Meta-Analysis
Saturday, November 11, 2023
11:30 AM–01:00 PM
Abstract
Background:
Ototoxicity is considered as the dose limiting toxicity of cisplatin. Several DNA repair genes polymorphisms have been investigated for their association with cisplatin induced ototoxicity (CIO). However, the predictive value of these genetic variants is controversial. The aim of this study is to systemically review the literature pertaining to the potential genetic predisposition of DNA repair genes polymorphisms with CIO.
Methods:
PubMed, SCOPUS, web of science and trial registries were searched, we also extensively searched grey literature including OpenGrey, Web of Conferences and ProQuest Dissertations and Thesis Global. Moreover, we identified other potentially eligible studies by searching the reference lists of included studies. Q-genie tool was used for quality assessment. The systematic review was reported according to PRISMA guideline.
Results:
Eight studies were deemed eligible with a total of 672 subjects. The eight included studies investigated the association of CIO with nine DNA repair genes (XPA, XPC, ERCC1, ERCC2, XRCC1, EX01, ERCC4 and ERCC5). The total number of SNPs investigated were 96 SNPs among them 54 SNPs were of DNA repair genes. Among all SNPs studies, AC+CC genotypes of XPC rs2228001 was found to have otoprotective effect with decreased risk of CIO with OR 0.20 (0.06-0.70), P: 0.01. While the highest OR for increased CIO was identified when XPC rs2228001 was analysed in combination with SNPs in GSTP1, FASL or MSH3 genes with OR of 32.22, 22.29 and 17.09 respectively.
Discussion:
Several DNA repair genes polymorphisms and their associations with CIO have been explored in multiple studies. However, the findings are inconsistent and limited by the specific populations and SNPs studied in each article. More studies with larger sample sizes and standardized methodologies are needed to validate these findings and identify potential genetic markers that may aid in identifying patients who are at a higher risk of developing CIO.
Other: None
Presenting Author
Nabil Elhadi Omar BSc Pharm, BCOP, PharmD, PhD(C)National Centre for Cancer Care & Research- Hamad Medical Corporation
Authors
Rana Mekkawi BSc Pharm, PharmD
Qatar University
Anas Hamad PhD, MSc, RPh
HMC
Fatima Hawasly MD
Ambulatory Care Center (ACC), Hamad Medical Corporation
Hazem Elewa PhD, RPh, BCPS
Qatar University