Center of Breast Diseases and Department of Abdominal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Chin Med J (Engl). 2011 Jan;124(2):199-204.
Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.
One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods.
Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs.
GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.
尽管化疗是乳腺癌最重要的治疗方法之一，但由于个体间反应和毒性存在显著差异，其应用受到限制。表阿霉素（EPI）和环磷酰胺（CTX）的代谢主要由细胞色素 P450 酶（CYPs）和谷胱甘肽 S-转移酶（GSTs）介导。由于其遗传多态性，这些酶的活性在人群中呈多态性，这一点早已为人所知。本研究旨在探讨 CYP3A、GSTP1 和 MDR1 基因的遗传多态性对接受 EPI/CTX 化疗的乳腺癌患者治疗反应和不良反应的影响。
招募了 120 名 II 期或 III 期浸润性乳腺癌患者，每 2 周接受 3 至 4 个周期的 EPI 80 mg/m²和 CTX 600 mg/m²治疗。采用 AJCC TNM 分期系统（第六版）评估原发肿瘤和腋窝淋巴结的病理反应。采用 PCR-限制性片段长度多态性方法确定基因多态性的基因型。
携带 GSTP1（105）Ile/Val 或（105）Ile/Ile 基因型的患者更有可能获得良好的反应（OR，0.40；95%CI，0.16 - 0.96；P = 0.024）和较轻的毒性（OR，0.35；95%CI，0.13 - 0.78；P = 0.006），而携带（105）Val/Val 基因型的患者则不然。治疗反应与肿瘤的雌激素受体、孕激素受体和 Her2/neu 状态无关。未发现毒性作用与患者年龄、肿瘤分期、绝经状态和药物剂量强度之间存在相关性。
GSTP1 多态性与 EPI 和 CTX 方案的化疗反应或不良反应相关。
