Influence of chemotherapeutic drug-related gene polymorphisms on toxicity and survival of early breast cancer patients receiving adjuvant chemotherapy

被引:12
作者
Ludovini, Vienna [1 ]
Antognelli, Cinzia [2 ]
Rulli, Antonio [3 ]
Foglietta, Jennifer [1 ]
Pistola, Lorenza [1 ]
Eliana, Rulli [4 ]
Floriani, Irene [4 ]
Nocentini, Giuseppe [5 ]
Tofanetti, Francesca Romana [1 ]
Piattoni, Simonetta [6 ]
Minenza, Elisa [7 ]
Talesa, Vincenzo Nicola [2 ]
Sidoni, Angelo [8 ]
Tonato, Maurizio [9 ]
Crino, Lucio [10 ]
Gori, Stefania [11 ]
机构
[1] Azienda Osped Perugia, S Maria della Misericordia Hosp, Med Oncol Div, Perugia, Italy
[2] Univ Perugia, Dept Expt Med, Piazzale Menghini 8-9, I-06156 Perugia, Italy
[3] Univ Perugia, Dept Surg, Breast Unit, Perugia, Italy
[4] IRCCS, Ist Ric Farmacol Mario Negri, Oncol Dept, Milan, Italy
[5] Univ Perugia, Dept Med, Sect Pharmacol, Perugia, Italy
[6] Univ Perugia, Haematol Dept, Perugia, Italy
[7] S Maria Hosp, Med Oncol Div, Terni, Italy
[8] Univ Perugia, Med Sch, Sect Anat & Histol, Dept Expt Med, Perugia, Italy
[9] Umbria Reg Canc Network, Perugia, Italy
[10] IRCCS, Ist Sci Romagnolo Studio Cura Tumori IRST, Med Oncol, Meldola, Italy
[11] SacroCuore Don Calabria Hosp, Med Oncol, Verona, Italy
关键词
Early breast cancer; Polymorphisms; Adjuvant chemotherapy; Toxicity; Prognosis; FOLATE CARRIER GENE; METHOTREXATE TREATMENT; PHARMACOGENETICS; REGION; GSTM1; 80G-GREATER-THAN-A; CYCLOPHOSPHAMIDE; HOMOCYSTEINE; ISOENZYMES; SEQUENCES;
D O I
10.1186/s12885-017-3483-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:11
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