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首页> 外文期刊>BMC Cancer >Influence of chemotherapeutic drug-related gene polymorphisms on toxicity and survival of early breast cancer patients receiving adjuvant chemotherapy
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Influence of chemotherapeutic drug-related gene polymorphisms on toxicity and survival of early breast cancer patients receiving adjuvant chemotherapy

机译：化疗药物相关基因多态性对早期辅助化疗的乳腺癌患者毒性和生存的影响

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Background We investigated whether GSTT1 (“null” allele ) , GSTM1 (“null”allele ) , GSTP1 (A313G), RFC1 (G80A), MTHFR (C677T), TS (2R/3R) polymorphisms were associated with toxicity and survival in patients with early breast cancer (EBC) treated with adjuvant chemotherapy (CT). Methods This prospective trial included patients with stage I–III BC subjected to CT with CMF or FEC regimens. PCR-RFLP was performed for MTHFR, RFC1 and GSTP1 , while PCR for TS, GSTT1 and GSTM1 genes. Results Among the 244 patients consecutively enrolled, 48.7% were treated with FEC and 51.3% with CMF. Patients with TS2R/3R genotype showed less frequently severe neutropenia (G3/G4) than those with TS2R/2R and 3R/3R genotype ( p =?0.038). Patients with MTHFRCT genotype had a higher probability of developing severe neutropenia than those with MTHFR CC genotype ( p =?0.043). Patients with RFC1GG or GSTT1-null genotype or their combination ( GSTT1-null/RFC1GG) were significantly associated with a shorter disease free survival (DFS) ( p =?0.009, p =?0.053, p =?0.003, respectively) and overall survival (OS) ( p =?0.036, p =?0.015, p =?0.005, respectively). Multivariate analysis confirmed the association of RFC1GG genotype with a shorter DFS ( p =?0.018) and of GSTT1-null genotype of a worse OS ( p =?0.003), as well as for the combined genotypes GSTT1-null/RFC1GG, (DFS: p =?0.004 and OS: p =?0.003). Conclusions Our data suggest that TS2R/2R and 3R/3R or MTHFR CT genotypes have a potential role in identifying patients with greater risk of toxicity to CMF/FEC and that RFC1 GG and GSTT1-null genotypes alone or in combination could be important markers in predicting clinical outcome in EBC patients.
机译：背景我们研究了GSTT1（“无效”等位基因），GSTM1（“无效”等位基因），GSTP1（A313G），RFC1（G80A），MTHFR（C677T），TS（2R / 3R）多态性是否与患者的毒性和生存率相关辅助化疗（CT）治疗的早期乳腺癌（EBC）。方法这项前瞻性试验包括接受CMF或FEC方案的CT的BC期I–III期患者。对MTHFR，RFC1和GSTP1执行PCR-RFLP，对TS，GSTT1和GSTM1基因进行PCR。结果连续纳入的244例患者中，接受FEC治疗的占48.7％，接受CMF治疗的占51.3％。与TS2R / 2R和3R / 3R基因型的患者相比，TS2R / 3R基因型的患者出现严重中性粒细胞减少症（G3 / G4）的频率更低（p =？0.038）。 MTHFRCT基因型的患者发生严重中性粒细胞减少的可能性高于MTHFR CC基因型的患者（p =？0.043）。具有RFC1GG或GSTT1-null基因型或其组合（GSTT1-null / RFC1GG）的患者与较短的无病生存期（DFS）显着相关（分别为p = 0.009，p = 0.053，p = 0.003）和总体生存（OS）（分别为p =？0.036，p =？0.015，p =？0.005）。多变量分析证实RFC1GG基因型与较短的DFS（p =？0.018）和OS较差的GSTT1-null基因型（p =？0.003）以及组合基因型GSTT1-null / RFC1GG（DFS）的相关性：p ＝ 0.004，OS：p ＝ 0.003）。结论我们的数据表明，TS2R / 2R和3R / 3R或MTHFR CT基因型在鉴定对CMF / FEC有更高毒性风险的患者中具有潜在作用，并且单独或组合使用的RFC1 GG和GSTT1空基因型可能是预测EBC患者的临床结局。

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