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Drug-related genetic polymorphisms affecting severe chemotherapy-induced neutropenia in breast cancer patients

机译：药物相关的遗传多态性影响乳腺癌患者严重的化疗引起的中性粒细胞减少

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Chemotherapy-induced neutropenia (CIN) is one of the major adverse events that necessitate chemotherapy dose reduction. This study aimed to evaluate the association between grade 4 neutropenia and genetic polymorphisms in breast cancer patients. In this genetic polymorphism association study, peripheral blood samples from 100 consecutive breast cancer outpatients, between August 2012 and September 2014, treated with doxorubicin and cyclophosphamide (AC) combination chemotherapy were genotyped for polymorphisms in adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), cytochrome P450 (CYP) enzyme-coding genes (CYP2B6 and CYP3A5), glutathione S-transferase (GST), and excision repair cross-complementing 1 (ERCC1). Associations between grade 4 neutropenia and genotypes as well as risk factors were examined using multivariate logistic regression. From 100 patients, 32.0% had grade 4 neutropenia. Multivariate logistic regression analysis revealed that ERCC1 118C > T (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.22–9.69; P = 0.020), CYP2B6∗6 (OR, 4.51; 95% CI, 1.21–16.95; P = 0.025), body mass index (BMI) (OR, 6.94; 95% CI, 1.15–41.67; P = 0.035), and baseline white blood cell (WBC) count (OR, 2.99; 95% CI, 1.06–8.40; P = 0.038) were significant predictors of grade 4 neutropenia. ERCC1 and CYP2B6 gene polymorphisms were associated with the extent of grade 4 neutropenia in patients receiving AC chemotherapy. In addition to previously known risk factors, BMI and WBC counts, ERCC1 and CYP2B6 gene polymorphisms were also identified as independent strong predictors of grade 4 neutropenia.
机译：化疗引起的中性粒细胞减少症（CIN）是必须减少化疗剂量的主要不良事件之一。这项研究旨在评估乳腺癌患者4级中性粒细胞减少与遗传多态性之间的关联。在这项遗传多态性关联研究中，对2012年8月至2014年9月之间接受多柔比星和环磷酰胺（AC）联合化疗的100位连续乳腺癌门诊患者的外周血样本进行了基因型分析，确定三磷酸腺苷结合盒B亚家族B成员1（ABCB1 ），细胞色素P450（CYP）酶编码基因（CYP2B6和CYP3A5），谷胱甘肽S-转移酶（GST）和切除修复交叉互补1（ERCC1）。使用多因素logistic回归分析了4级中性粒细胞减少症与基因型和危险因素之间的关联。在100名患者中，有32.0％患有4级中性粒细胞减少症。多元logistic回归分析显示ERCC1 118C> T（比值[OR]，3.43； 95％置信区间[CI]，1.22-9.69； P = 0.020），CYP2B6 * 6（OR，4.51； 95％CI，1.21– 16.95； P = 0.025），体重指数（OR，6.94； 95％CI，1.15-41.67； P = 0.035）和基线白细胞（WBC）计数（OR，2.99； 95％CI，1.06） –8.40； P = 0.038）是4级中性粒细胞减少的重要预测指标。 ERCC1和CYP2B6基因多态性与接受AC化疗的患者的4级中性粒细胞减少程度有关。除先前已知的危险因素外，BMI和WBC计数，ERCC1和CYP2B6基因多态性也被确定为4级中性粒细胞减少症的独立强预测指标。

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