| Objective:To better understanding the distribution and other characteristics of methylenetetrahydrofolate reductase(MTHFR)gene polymorphisms in female breast cancer patients and normal population in Yunnan province,and also for enriching gene polymorphism database in different regions of China to identify nutritional dietary factors for breast diseases,and the role of development provides new ideas for the prevention and treatment of breast cancer as well.Methods:Case-control study was used to collect blood samples from 980 patients and healthy volunteers on the basis of previous studies.Whole blood DNA was extracted and the candidate SNPs of MTHFR were selected and used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS)screening results,combined with patient clinical information and laboratory test results,to analyze the subgroup differences.Results:1.According to the case-control design,a total of 980 cases were included in the study and 1:1 was allocated to the experimental and control groups(n=490).After adjusting the baseline level,the average age was 47.68±9.86 years and 48.01±7.98 years respectively.After testing,the populations of the two groups of samples did not differ from each other(P=0.322).2.A Hardy-Weinberg equilibrium test was performed on the UTR of the 3’UTR region and the 18 candidate SNPs in the coding region of the MTHFR.The TREND method was used to calculate the rs17884306(P=0.0037)and rs1801394(P=0.0040)for the experimental group and health.There were differences in the control group;the REC method calculated rs1801394(P=0.0196)and the DOM method calculated rs17884306(P=0.0289)when the two groups of data were different.The remaining points and methods did not show differences in the two groups.3.According to molecular typing and hormone receptor typing,the distribution of rs1801394 polymorphism G/A locus genotypes in healthy and breast cancer patients was found to be different(OR=0.825,95%CI=0.733-0.917,P=0.004);The distribution of rs17884306 gene polymorphism C/G locus in healthy and breast cancer patients showed no difference(OR=0.653,95%CI=0.202-1.104,P=0.076).4.rs1801394 is associated with HER-2 positive breast cancer in molecular typing.Patients with GG polymorphism in this site have a 44%higher risk of breast cancer than those with AG/AA polymorphism(OR=0.568,95.%CI=0.262-0.874,P=0.042).No difference was found between the other subtypes(Luminal A:OR=0.685,95%CI=0.313-1.057,P=0.685;Luminal B:OR=0.952,95%CI.=0.736-1.168,P=0.254;TNBC:OR=0.842,95%CI=0.537-1.147,P=0.754).5.rs1801394 was not associated with ER-positive,ER-negative,PR-positive and PR-negative breast cancers in hormone receptor typing.There was no difference between the two groups in subtype analysis(ER Positive:OR=0.841,95%CI=0.605-1.277,P=0.324;ER Negative:OR=0.892,95%CI=0.542-1.142,P=0.331;PR Positive:OR=0.842,95%CI=0.608-1.076,P=0.629;PR Negative:OR= 0.819,95%CI=0.514-1.104,P=0.282).6.Whether the rs17884306 loci are molecular typing or hormone receptor typing,there is no statistical difference in the risk of breast cancer between CC-type and GC/GG-type people(Luminal A:OR=0.636,95%CI=0.206-1.066,P=0.359;Luminal B:OR=0:656,95%CI=0.305-1.007,P=0.198;HER-2:OR=0.788,95%CI=0.458-1.118,P=0.225;While TNBC patients have the number of:ORF=0.881,95%CI=0.391-1.371,P=0.333;ER Positive patients:OR=0.619,95%CI=0.155-1.083,P=0.945;ER Negative:OR=0.787,95%CI=0.087-1.887,P= 0.862;PR Positive:OR = 0.826,95%CI=0.533-1.119,P= 0.384;PR Negative:OR = 0.895,95%CI=0.65-1.155,P = 0.691).7.In the overall patient and subgroup analysis,only "tumor size" and subgroup differences between the two gene frequency populations(OR=2.127,95%CI=1.172-3.862,Tumor≤ 5 P=0.016,>5 P=0.012).No differences in the other two groups were shown.Statistically stratified by molecular typing,the overall patient’s difference was contributed by patients with greater than 5 cm in Luminal type B patients(OR=0.585,95%CI=0.379-0.891,P=0.042),and the remaining subtypes None of these subgroups had such differences.8.The clinical laboratory test results of patients were classified into Ref SNP rs17884306 and rs1801394 for association and risk analysis.There was no correlation between the patient’s indicators and their gene polymorphisms,and there was no evidence that there was a difference in the frequency of the two genes.Conclusion:The Ref SNP rs1801394 and rs17884306 screened out in the experimental group and the control group were balanced with the breast cancer;the rest of the points and methods did not show the difference between the two groups.The results of dominant genetic model analysis showed that the distribution of rs1801394 gene polymorphism G/A locus genotype was different in healthy and breast cancer patients(OR=0.825,95%CI=0.733-0.917,P=0.004);rsl7884306 There was no difference in the distribution of gene polymorphism C/G locus genotype between healthy and breast cancer patients(OR=0.653,95%CI=0.202-1.104,P=0.076).Rs1801394 is associated with HER-2 positive breast cancer in molecular typing.Patients with GG polymorphism in this site have a 44%higher risk of breast cancer than those with AG/AA polymorphism(OR=0.568,95%CI=0.262-0.874,P=0.042).No differences were found between the other subtypes and hormone receptor typing types.The molecular typing of rs17884306 and hormone receptor typing were both in CC and GC/GG populations.No statistical difference.The overall"tumor size" and subgroup differences between the two gene frequency populations(OR = 2.127,95%CI=1.172-3.862,P<0.05),the remaining characteristics did not show two groups of differences,visible patients No correlation was found between the indicators and their gene polymorphisms,and there was no evidence that there was a difference in the frequency of the two genes. |
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