Association Between Single Nucleotide Polymorphisms Of CYP19A1 And Lipid Profiles Impacted By Non-steroidal Aromatase Inhibitors In Postmenopausal Women With Breast Cancer

ObjectiveTen single nucleotide polymorphisms(SNPs)of CYP19A1,CYP1B1,CYP2B6,CYP2C9,ESR1,ESR2 and FABP4 genes were determined by microfluidic method,and their correlation with pathological features of breast cancer was studied.We analysis the Changes in blood lipids after 6 months of non-steroidal aromatase inhibitors(AIs)in estrogen receptor(ER)positive postmenopausal breast cancer patients and the correlation between SNPs and AIs-induced changes in blood lipids.Methods(1)Collecting tumor tissue specimens and clinicopathological data of 396 female breast cancer patients who were hospitalized from September 2016 to February 2018 in the the PLA General Hospital Hospital.Using the BioMark HD gene analysis system to detect ten SNPs including CYP19A1 rs2470152,CYP19A1 rs700519,CYP19A1 rs727479,CYP1B1 rs1056836,CYP2B6 rs4802101,CYP2C9 rs4918766,ESR1 rs2234693,ESR1 rs2273206,ESR2 rs2987983,and FABP4 rs1054135.Their correlation with pathological features of breast cancer was analyzed.(2)Follow-up of patients with ER receptor-positive postmenopausal breast cancer,and collect endocrine therapy and fasting lipid test results 6 months after endocrine therapy,including total cholesterol(TC),triglyceride(TG),low-density lipid Protein(LDL),high density lipoprotein(HDL).Compared with preoperative blood lipids,the effects of AIs treatment on blood lipids were analyzed,and the correlation between age,body mass index(BMI),blood lipid levels before AIs treatment and blood lipid changes were analyzed.(3)The association of SNPs and AIs treatment induced TC,TG,LDL and HDL were studied by one-way analysis of variance and multiple linear regression analysis.Results(1)358 breast cancer patients successfully performed SNPs and obtained complete clinical and pathological data.Multivariate analysis showed that the correlation between CYP2C9 rs4918766 and ESR1 rs2273206 and axillary lymph node metastasis was statistically significant(P<0.05).The risk of axillary lymph node metastasis was lower in rs4918766 G/G than in A/G(P=0.027).The rs2273206 T/T type had a lower risk of axillary lymph node metastasis than G/T(P=0.010).(2)86 postmenopausal ER-positive breast cancers were followed up for serum lipids after 6 months of treatment with non-steroidal AIs.Compared with preoperative blood lipids,TC increased(0.29±0.70)mmol/L,LDL increased(0.32±0.54)mmol/L,and the changes were statistically significant(P<0.05).There was no statistical change in TG and HDL.Learning differences(P>0.05).Univariate analysis showed that there was a very weak correlation between the degree of change before and after TC treatment and the pre-treatment LDL level(r=-0.242,P=0.024).The degree of change before and after LDL treatment was negatively correlated with pre-treatment LDL levels(r=-0.475,P<0.001),and negatively correlated with pre-treatment TC levels(r=-0.228,P<0.035).In the multivariate analysis of factors affecting LDL change values,pre-treatment TC and pre-treatment LDL were included in multiple linear regression analysis(stepwise method).The results showed that LDL changes were negatively correlated with pre-treatment LDL levels(r2=0.226,P<0.001)There was no statistically significant association with pretreatment TC levels(P=0.769).(3)In FABP4 rs1054135,the elevation of TC was significantly higher in A/A type(+0.54 mmol/L)than in A/G type(+0.18 mmol/L)and G/G type(-0.05 mmol/L).Statistical differences(P<0.05)were showed by one-way anova and multiple Linear regression analysis.Multivariate analysis showed that the level of LDL increase was correlated with CYP19A1 gene rs2470152 and ESR1 gene rs2234693.The LDL increase of rs2470152 T/T type was not obvious,while that of rs2234693 CC type was obvious.One-way analysis of variance showed that there were statistically significant differences in LDL changes between different SNPs types(P=0.018).The LDL level of T/T type was only increased by 0.11mmol/L,while that of C/C type and C/T type was increased by 0.45mmol/L and 0.41 mmol/L,respectively.The difference in LDL level between T/T type and C/T type was statistically significant(P=0.021).There was no statistically significant difference in the degree of change between T/T type and C/C type(P=0.904).In the one-way anova of rs2234693 and the comparison between C/C type and the other two types,there was no statistically significant difference in the degree of LDL increase(P>0.05).Conclusions(1)The polymorphisms of CYP2C9 gene rs4918766 and ESR1 gene rs2273206 were associated with axillary lymph node metastasis.The risk of axillary lymph node metastasis in rs4918766 G/G type was lower than in A/G type,and the risk of axillary lymph node metastasis in rs2273206 T/T type was lower than in G/T type.(2)Non-steroidal AIs can cause rise in TC and LDL.The degree of LDL increase is negatively correlated with the level of LDL before treatment.LDL level before treatment is an independent predictor of the degree of LDL change.(3)The polymorphisms of CYP19A1 gene rs2470152 were correlated with the changes of LDL before and after the treatment of non-steroidal AIs.The polymorphisms of T/T type were slightly higher than those of C/T type.