Roles of pharmacogenomics in non-anthracycline antineoplastic-induced cardiovascular toxicities: A systematic review and meta-analysis of genotypes effect

• Main Authors: Siew Lian Leong, Nathorn Chaiyakunapruk, Wichittra Tassaneeyakul, Poukwan Arunmanakul, Surakit Nathisuwan, Shaun Wen Huey Lee
• Other Authors: Taylor's University Malaysia
• Format: Article
• Published: 2020
• Subjects: Medicine
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/51777
• Institution: Mahidol University

© 2018 Elsevier B.V. Background: Exploration on genetic roles in antineoplastic-related cardiovascular toxicity has increased with the advancement of genotyping technology. However, knowledge on the extent of genetic determinants in affecting the susceptibility to the cardiovascular toxicities of antineoplastic is limited. This study aims to identify potential single nucleotide polymorphism (SNP) in predicting non-anthracycline antineoplastic-related cardiovascular toxicity. Methods: We systematically searched for original research in PubMed, Cochrane Central Register of Controlled Studies, CINAHL Plus, EMBASE and HuGE Navigator from database inception until January 2018. Studies on association between polymorphism and antineoplastic-induced cardiovascular toxicity in patients treated for cancer of all antineoplastic agents were included except for anthracycline. Case reports, conference abstracts, reviews and non-patient studies were excluded. Data extracted by two independent reviewers were combined with random-effects model and reported according to PRISMA and MOOSE guidelines. Results: The 35 studies included examined a total of 219 SNPs in 80 genes, 11 antineoplastic and 5 types of cardiovascular toxicities. Meta-analyses showed that human epidermal growth factor receptor 2 (HER2) rs1136201, a risk variants (pooled OR: 2.43; 1.17–5.06, p = 0.018) is a potential predictors for trastuzumab-related cardiotoxicity. Gene dose effect analysis showed number of variant allele may contribute to the risk too. Conclusions: This review found that HER2 rs1136201 can have the potential in predicting trastuzumab-related heart failure. As such, further studies are needed to confirm the validity of these results as well as determine the economic aspect of using SNPs prior to its implementation as a clinical practice.