Key result
Six genetic variants, including HER2-Ile655Val rs1136201 (OR 2.48), were significantly associated with an increased risk of chemotherapy-induced cardiotoxicity in cancer patients.
Why the study?
Chemotherapy-induced cardiotoxicity remains a major clinical concern, prompting evaluation of whether genomic variants correlate with risk of cardiotoxicity.
Do specific genetic variants increase the risk of chemotherapy-induced cardiotoxicity in cancer patients?
Meta-Analysis (n=9,183)
Do specific genetic variants increase the risk of chemotherapy-induced cardiotoxicity in cancer patients?
Odds Ratio: 2.48 (95% CI 1.53–4.02)
p-value: p=0.0002
Specific genetic variants, including those in CYBA, RAC2, CYP3A5, ABCC1, ABCC2, and HER2, are significantly associated with an increased risk of chemotherapy-induced cardiotoxicity, highlighting the potential for pharmacogenomic risk screening.
May support pharmacogenomic screening to stratify cardiotoxicity risk before chemotherapy; extends genetic association data but requires prospective validation.
Chemotherapy is widely used in the treatment of cancer patients, but the cardiotoxicity induced by chemotherapy is still a major concern to most clinicians. Currently, genetic methods have been used to detect patients with high risk of chemotherapy-induced cardiotoxicity (CIC), and our study evaluated the correlation between genomic variants and CIC. The systematic literature search was performed in the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), China Biology Medicine disc (CBMdisc), the Embase database, China National Knowledge Internet (CNKI) and Wanfang database from inception until June 2020. Forty-one studies were identified that examined the relationship between genetic variations and CIC. And these studies examined 88 different genes and 154 single nucleotide polymorphisms (SNPs). Our study indicated 6 variants obviously associated with the increased risk for CIC, including CYBA rs4673 (pooled odds ratio, 1.93; 95% CI, 1.13-3.30), RAC2 rs13058338 (2.05; 1.11-3.78), CYP3A5 rs776746 (2.15; 1.00-4.62) ABCC1 rs45511401 (1.46; 1.05-2.01), ABCC2 rs8187710 (2.19; 1.38-3.48), and HER2-Ile655Val rs1136201 (2.48; 1.53-4.02). Although further studies are required to validate the diagnostic and prognostic roles of these 6 variants in predicting CIC, our study emphasizes the promising benefits of pharmacogenomic screening before chemotherapy to minimize the CIC.
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Yang et al. (2021) conducted a meta-analysis in Chemotherapy-induced cardiotoxicity (n=9,183). HER2-Ile655Val rs1136201 variant vs. Non-carriers / Wild-type was evaluated on Chemotherapy-induced cardiotoxicity (OR 2.48, 95% CI 1.53-4.02, p=0.0002). Six genetic variants, including HER2-Ile655Val rs1136201 (OR 2.48), were significantly associated with an increased risk of chemotherapy-induced cardiotoxicity in cancer patients.
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