Prognostic Impact of CYP2B6 Q172H and K262R Polymorphism on Breast Cancer Patients Treated with Cyclophosphamide-based Adjuvant Chemotherapy

Abstract: Objective to study the effect of rotary magnetic field (RMF) combining 5-Fu on the cycle and apoptosis of mouse cell line SP2/0 in vitro. Methods SP2/0 cells were randomly divided into four groups: control group (N), 5-Fu group (C), magnetic group (M) and magnetic combining 5-Fu group (M+C).The M and M+C groups were treated with a RMF for two hours once a day.On day 4, the C and M+C groups were treated with 5-Fu 20 μg/ml.On day 5, cell cycle and apoptosis were measured by the flow cytometric (FCM). Results The S phase proportion of the M group and the G1 phase proportion of the C group were higher than that of the other three groups（P<0.05）.The S phase proportion of the M+C group decreased and lower than that of the M group，but was still higher than that of the N and C groups（P<0.05）.There was no significant difference in apoptosis rates between the N and M groups（P>0.05）.The apoptosis rates of the C and M+C groups were remarkedly higher than those of the N and M groups and the M+C group had the highest apoptosis rate. Conclusion The RMF can't induce the apoptosis.But it can enhance the cytotoxicity of 5-Fu and promote the cell apoptosis.The mechanism of the apoptosis may be related to SP2/0 cell line arrested at S phase.Objective To investigate the association of CYP2B6 Q172H and K262R polymorphisms with clinical outcome of breast cancer patients treated with cyclophosphamide-based adjuvant chemotherapy. Methods A total of 100 patients with breast cancer were recruited.All patients received cyclophosphamide-based adjuvant chemotherapy.PCR-LDR (ligation detection reaction) method was used to detect genotypes of CYP2B6 Q172H and K262R. Results Of the 100 patients, the prevalence of the Q172H(516G>T) GG,GT and TT genotype was 59%,38% and 3%, respectively, and the frequencies of K262R(785A>G) AA,AG and GG genotype was 47%,43% and 10%,respectively.The recurrence-free survival rate in patients with Q172H GT and TT genotype were significantly higher than those in patient s with GG genotype （P<0.05).Also, the recurrence-free survival rate in patient s with K262R AG and GG genotype were significantly higher than those in patient s with AA genotype (P<0.05).However, multivariable analysis showed that only Q172H GT and TT genotype were associated with shorter recurrence-free survival (P<0.05). Conclusion Polymorphism of Q172H GT and TT may be a potential prognostic factor in breast cancer patients treated with cyclophosphamide-based adjuvant chemotherapy.