Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita City, Osaka 565-0871, Japan.
Breast Cancer Res Treat. 2012 Apr;132(3):947-53. doi: 10.1007/s10549-011-1637-5. Epub 2011 Jun 25.
The aim of this study was to investigate the association of two genetic polymorphisms, MDM2 SNP309 and TP53 R72P, with incidence of neutropenia in breast cancer patients treated with 5-FU/epirubicin/cyclophosphamide (FEC). Primary breast cancer patients (n = 216) treated with adjuvant FEC (60, 75 or 100 mg/m(2)) were included in this study. The association of genotypes of MDM2 SNP309 and TP53 R72P, determined by TaqMan SNP Genotyping Assays, with febrile neutropenia (FN) was investigated. In the patients treated with FEC100, G/G genotype for MDM2 SNP309 (G/G genotype( MDM2 )) was significantly (P < 0.01) associated with a lower incidence (5.3 vs. 39.2%) of severe neutropenia (<100/mm(3)) than with T/T + T/G genotypes( MDM2 ), and C/C genotype for TP53 R72P (C/C genotype( TP53 )) was significantly (P = 0.03) associated with a higher incidence (58.3 vs. 27.3%) of FN than with G/G + G/C genotypes( TP53 ). The combination of C/C genotype( TP53 ) and T/T + T/G genotype( MDM2 ) showed the highest risk for developing severe neutropenia (83.3%) and FN (62.5%) than any other combinations. In the patients treated with FEC60 or FEC75, there was no significant association of MDM2 SNP309 and TP53 R72P with severe neutropenia and FN. MDM2 SNP309 and TP53 R72P are significantly associated with severe neutropenia and FN, respectively, in breast cancer patients treated with FEC100, and especially their combination may be a useful predictor of severe neutropenia and FN.
本研究旨在探讨 MDM2 SNP309 和 TP53 R72P 这两种基因多态性与接受氟尿嘧啶/表柔比星/环磷酰胺（FEC）治疗的乳腺癌患者中性粒细胞减少症发生率的相关性。本研究纳入了 216 例接受辅助 FEC（60、75 或 100mg/m2）治疗的原发性乳腺癌患者。通过 TaqMan SNP 基因分型检测，分析了 MDM2 SNP309 和 TP53 R72P 基因型与发热性中性粒细胞减少症（FN）的关系。在接受 FEC100 治疗的患者中，MDM2 SNP309 的 GG 基因型（MDM2 GG 基因型）与严重中性粒细胞减少症（<100/mm3）的发生率（5.3%比 39.2%）显著降低相关（P<0.01），而 TT+TG 基因型（MDM2 TT+TG 基因型）；TP53 R72P 的 CC 基因型（TP53 CC 基因型）与 FN 的发生率（58.3%比 27.3%）显著升高相关（P=0.03），而 GG+GC 基因型（TP53 GG+GC 基因型）。与任何其他组合相比，TP53 CC 基因型与 MDM2 TT+TG 基因型的组合发生严重中性粒细胞减少症（83.3%）和 FN（62.5%）的风险最高。在接受 FEC60 或 FEC75 治疗的患者中，MDM2 SNP309 和 TP53 R72P 与严重中性粒细胞减少症和 FN 无显著相关性。在接受 FEC100 治疗的乳腺癌患者中，MDM2 SNP309 和 TP53 R72P 分别与严重中性粒细胞减少症和 FN 显著相关，特别是它们的组合可能是严重中性粒细胞减少症和 FN 的一个有用预测因子。
