Allelic variant 6A (rs35068180) of the MMP-3 promoter region as a predictor of cardiotoxicity after the end of adjuvant chemotherapy with doxorubicin in patients with breast cancer

Abstract

Aim. To evaluate the relationship of polymorphic variants rs2232228 of the HAS3 gene, rs8187710 of the ABCC2 gene, rs35068180 of the MMP-3 gene with cardiotoxicity after the end of adjuvant chemotherapy in patients with breast cancer.Material and methods. The study included 100 patients (women, mean age 52,5±9,4 years) diagnosed with breast cancer who received anthracycline antibiotics (doxorubicin, total dose 240 mg/m2 or 360 mg/m2). Echocardiography was performed before and after the end of chemotherapy. Polymorphic status of selected targets was determined using the real-time polymerase chain reaction.Results. After the end of chemotherapy, based on the changes of left ventricular ejection fraction and global longitudinal strain, cardiotoxicity (CT) was detected in 20 patients. There were following significant differences between subgroups: rs8187710 of the ABCC2 gene — not identified; rs2232228 of the HAS3 gene — genotype AA, odds ratio (OR) 3,37 (95% confidence interval (CI) 1,14; 9,97) and allelic variant A, OR 2,17 (95% CI 0,98; 4,80) are significantly more common (p<0,05) in the cardiotoxicity+ subgroup; rs35068180 of the MMP-3 gene — genotype 6A/6A, OR 2,53 (95% CI 0,93; 6,88) and allelic variant 6A, OR 2,19 (95% CI 1,08; 4,44) are significantly more often (p<0,05) in the cardiotoxicity+ subgroup.Conclusion. Genotype 6A/6A, allelic variant 6A rs35068180 of the MMP-3 gene, genotype AA and allelic variant A rs2232228 of the HAS3 gene can be considered as predictors of early cardiotoxicity after the end of chemotherapy in patients with breast cancer receiving doxorubicin.

Keywords

• breast cancer
• cardiotoxicity
• anthracyclines
• doxorubicin
• metalloproteinases
• rs35068180 of the mmp-3 gene
• rs2232228 of the has3 gene
• rs8187710 of the abcc2 gene
• echocardiography