The HER2 655 A>G genetic variant has recently been associated with trastuzumab-induced cardiotoxicity in HER2 breast cancer patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the cardiac toxicity of trastuzumab in breast cancer patients. Our study population was composed of 78 HER2 breast cancer patients receiving trastuzumab. The HER2 655 A>G (rs1136201) genetic variant was genotyped using TaqMan allelic discrimination technology. Patients were classified on the basis of the occurrence of cardiotoxic events or the absence of cardiotoxic events during 1 year after the first infusion. The HER2 655 A>G polymorphism was significantly associated with cardiotoxicity: AG versus AA [P=0.012, odds ratio (OR)=5.12, 95% confidence interval (CI) 1.43-18.36], AG+GG versus AA (P=0.01, OR=5.72, 95% CI 1.50-21.76), AG versus AA+GG (P=0.005, OR=7.17, 95% CI 1.82-28.29). A meta-analysis combining these data with the results from previous studies confirmed this association. Our results support the role of the HER2 655 A>G polymorphism as a genetic marker of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.

BackgroundThe IL-6 -174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA.Materials and methodsOur study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 -174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion.ResultsThe -174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29-6.70], 18 (P=4.54E-03, OR=5.17, 95% CI 1.80-14.85), and 24 months (P=4.54E-03, OR=14.86, 95% CI 2.91-75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E-02, OR=1.80, 95% CI 1.13-2.87, at 12 months).ConclusionOur results support the role of the -174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.