The Relationship Between BRCA1 And Susceptible Gene Polymorphism And Characteristic Of Ultrasound In Sporadic And Familial Breast Cancer In Chinese Female Of The Zhuang Nationality

Part One Association of single nucleotide polymorphisms of BRCA1 and related genes in sporadic breast cancer in Chinese female of Guangxi Zhuang NationalityOBJECTIVEBreast cancer is the very common malignant tumor in females,and the recent data indicated that the breast cancer is the most common malignant tumor in females in Guangxi province.The mechanism underlying the genesis and the development of the breast cancer is unclear.It is considered that breast cancer is related to the synergistic action of multiple genes,and the main reason is the malfunction of cancer gene and tumor suppressor gene.It has been proved that BRCA 1 gene is the one of most susceptible gene and it is highly related with the risk of breast cancer.Besides BRCA1,SLC4A7 and ESR 1 are also related with breast cancer.Single nucleus polymorphism is the one of main characteristics of BRCA1 and the genesis of breast cancer.Therefore,it is of great importance to exploring the relationship between SNP and the mechanism of breast cancer.To investigate the role of BRCA1 and related susceptibility gene single nucleotide polymorphism loci distributing in thegenesis and development of breast cancer in Zhuang population in Guangxi,case control study was used,and 20 sites of BRCA1 gene were analyzed.Theresults of our study will be helpful to the early screen and primary prevention of sporadic breast cancer.We selected 288 patients with breast cancer who were treated in the First Affiliated Hospital of Guangxi Medical University from January 2009 to December 2015,and 600 healthy women served as control group.After the extraction of DNA,the samples were detected by Taq Man probe real-time fluorescence quantitative PCR.The characteristic of susceptible genes and the relationship between SNP of the BRCA1 and related susceptibility genes and the prevalence of sporadic breast cancer in Guangxi Zhuang population was analyzed.RESULTIn this study,20 detection sites were selected,and the genotyping uccess rate was 98%.All tested loci showed polymorphism.Except the site s1078806,the frequency distributions of the other nineteen loci were in line with the Hardy-Weinberg equilibrium,P< 0.05.The distribution of rs799906,rs4973768,rs3757318,rs2046210 showed significant difference between control group and patients with breast cancer.The distribution of other sites showed no significant difference between two groups.The distribution frequency of rs799906,TC,TT and CC in the breast cancer group was 58/129/101,and the distribution frequency was 60/270/270 in the normal control group,which was consistent with the dominant genetic model and the super dominant genetic model.OR value(OR value 0.64,95%CI: 0.53-0.80,P<0.05).TC genotype frequency was significantly different among breast cancer patients with axillary lymph node metastasis and no axillary lymph node metastasis.TC genotype frequencies in the axillary lymph node metastasis group were as high as 61.11%(55/90),and37.37%(74/198)in no axillary lymph node metastasis group,(OR value 1.77,95% CI:1.24-2.5,P<0.05).The distribution of rs4973768,CC TC,TT genotype in breast cancer group was 150/72/66,the distribution frequency in the control group was 402/150/48.This locus was in accord with the generalized genetic model,the dominant genetic model and the super dominant genetic model.OR value(95%CI)was1.76(1.45-2.14),P<0.05.The distribution frequencies of rs3757318,AA,AG,GG genotype in breast cancer group were 58/130/100,and 42/288/270 in control group.The site was in accord with the dominant genetic model and the super dominant genetic model(OR value 0.59,95%CI: 0.47-0.73,P< 0.05).The frequency of AG genotype of the rs3757318 was 34.60%(45/130)in the axillary lymph node metastasis group,and showed significant difference when compared with no axillary lymph node metastasis group(OR value 1.28,95%CI: 0.91-1.8,P< 0.05).The distribution frequency of rs2046210,CC,CT,TT genetype in the breast cancer groupwas 101/115/72,and 252/258/90 in the control group.This locus was in accordance with the generalized genetic model,the dominant genetic model,the recessive genetic model and the super dominant genetic model(OR value 1.37,95%CI: 1.13-1.66,P < 0.05).TT genotype frequencies of rs2046210 loci in the axillary lymph node metastasis group were as high as 50%(45/90)in the axillary lymph node metastasis group,and 28.79%(57/198)in no axillary lymph node metastasis group(OR value1.82,95%CI: 1.29-2.57,P<0.05).CONCLUSION:1.This study demonstrated that BRCA1 and related susceptibility gene single nucleotide polymorphism is associated with the incidence of female breast cancer in Guangxi Zhuang population.We found four associated sites:rs799906,rs4973768,rs3757318,rs2046210,which is located in BRCA1,slc4a7,ESRL and ESRL C6orf97 respectively.2.Breast cancer patients with the TC genotype of rs799906 locus,the AG genotype of the rs3757318 locus,the TT genotype of rs2046210 were at higher risk of axillary lymph node metastasis.Part Two Association of single nucleotide polymorphisms of BRCA1 and related genes in familial breast cancer in women of Guangxi Zhuang NationalityOBJECTIVE:The aim of this study was to explore the role of BRCA1 and susceptible gene single nucleotide polymorphism in thegenesis and development of in familial breast cancer in Guangxi Zhuang population.Case control study was used,and 20 sites of BRCA1 gene were analyzed.The results were compared to the patients group with sporadic breast cancer.Theresults of our study will be helpful to the early screen and primary prevention of familial breast cancer.METHODWe included 50 patients with familial breast cancer.The blood sample from the patients and their immediate families were collected.After the extraction of DNA,the samples were detected by Taq Man probe real-time fluorescence quantitative PCR.The characteristic of susceptible genes and the relationship between SNP of the BRCA1 and related susceptibility genes and the prevalence of sporadic breast cancer in Guangxi Zhuang population was analyzed.Patients with sporadic breast cancer served as control group.RESULTIn this study,20 detection sites were selected,and the genotyping success rate was 97.16%.All tested loci showed polymorphism.Except the site rs346425064 and rs346488663,the frequency distributions of the other eightteen loci were in line with the Hardy-Weinberg equilibrium.The distribution of rs799906,rs895745,rs4784227,rs3757318,rs4973768,rs2046210 showed significant difference between familial breast cancer group and control group.In patients with familial breast cancer,the gene rs799906 showed CC,TC,TT polymorphism.In the probands with C gene,the number of allele transmission was 33,non-transmission was 17;in the probands with T gene,the number of allele transmission was 17 and non-transmission was 33(x2=5.12,P =0.024).In patients with familial breast cancer in Guangxi Zhuang nationality of female,the gene rs895745 showed AG polymorphism.In the probands with A gene,the number of allele transmission was 34,non-transmission was 16;in the probands with G gene,the number of allele transmission was 16 and non-transmission was 34(x2=6.48,P =0.011).In patients with familial breast cancer in Guangxi Zhuang nationality of female,the gene rs478227 showed TC,TT polymorphism.In the probands with C gene,the number of allele transmission was 32,non-transmission was 18;in the probands with T gene,the number of allele transmission was 18 and non-transmission was 32(x2= 4.86,P =0.032).In patients with familial breast cancer in Guangxi Zhuang nationality of female,the gene rs3757318 showed AG,GG polymorphisms.In the probands with A gene,the number of allele transmission was 33,non-transmission was 17;in the probands with G gene,the number of allele transmission was 17 and non-transmission was 33(x2= 5.12,P =0.024).In patients with familial breast cancer in Guangxi Zhuang nationality of female,the gene rs4973768 showed CC,TC and TT polymorphisms.In the probands with C gene,the number of allele transmission was 35,non-transmission was 15;in the probands with T gene,the number of allele transmission was 15 and non-transmission was 35(x2= 8.00,P =0.005).In patients with familial breast cancer in Guangxi Zhuang nationality of female,the gene rs2046210 showed CC,TC and TT polymorphisms.In the probands with C gene,the number of allele transmission was 34,non-transmission was 16;in the probands with T gene,the number of allele transmission was 16 and non-transmission was 34(x2= 6.48,P =0.011).We found that rs799906-TC,rs895745-AG,rs2046210-TT,rs4784227-TC single nucleotide polymorphism is associated with hereditary breast cancer,whereas rs3757318-AG genotype is associated with sporadic breast cancer.CONCLUSION:1.This study found that BRCA1 and related susceptibility gene single nucleotide polymorphism is associated with the risk of female familial breast cancer in Guangxi Zhuang nationality,andidentified six positive loci: rs799906,rs895475,rs4784227,rs4973768,rs2046210,rs3757318.These 6 positive sites were located in 6 susceptibility genes and regions: BRCA1,WECA1-Brcc36,XRCA1,ESR1,T0X3,C6orf97,SLC4A7 gene.2.rs799906-TC,rs895745-AG,rs2046210-TT,rs4784227-TC single nucleotide polymorphism is associated with hereditary breast cancer,rs3757318-AG genotype is related to sporadic breast cancer.Part Three Characteristics of ultrasound imaging of familial and sporadic breast cancer in Guangxi Zhuang Nationality Woman and the Association of single nucleotide polymorphisms of BRCA1 and related susceptibility genesOBJECTIVEThe objective of this study was tocompare the characteristic of ultrasound imaging between familial and sporadic breast cancer and to investigate the relationship between the characteristics of ultrasound imaging of familial and sporadic breast cancer and the SNP of susceptibility genes.Our results will provide the informations to improve the diagnosis,treatment and prognosis of breast cancer.METHODThis study is performed in the female population in Guangxi area.We selected 100 patients with sporadic breast cancer and 40 patients with familial breast cancer who were treated in the First Affiliated Hospital of Guangxi Medical University from January 2009 to December 2015.All the patientsunderwent bilateral breast and axillary ultrasound examination before surgery.Clinical data and complete pathological information(including pathological type,histological grade and immunohistochemistry results of ER,PR,Cerb B2)were collected.After the extraction of DNA,the samples were detected by Taq Man probe real-time fluorescence quantitative PCR and the SNP of selected 20 susceptibility genes of breast cancer were examined.The sonographic features of sporadic and familial breast cancer were analyzed,and the correlations between ultrasound characteristics and SNP of tested genes were also analyzed.RESULT(1)This study included 140 patients,with an average age of 44.5 ± 11.2 years(from 21 to 72 years).Familial breast cancer group included 40 cases,aged 43.1± 10.6 years(from 21 to 65 years);sporadic breast cancer group included 100 cases,aged 45.7 ± 11.4 years(from 25 to 72 years).There was no significant difference in terms of age and pathological type between the two groups.The histological grade of TNM was significanthigher in FBC group than that of SBC group(U = 2018,P< 0.05).The expression of ER,PR and HER-2 showed no significant difference between the two groups.Ultrasound demonstrated that the incidence of microcalcifications was higher in FBC group than in the SBC group(P< 0.05),whereas the tumor size,morphology,aspect ratio,boundary,spiculation,no echo areaand hyperechoic halo sign showed no significant difference between two groups.There was no significant difference between the two groups in the comparison of CDFI blood flow and hemodynamic parameters.(2)BRCA1 and related susceptibility gene single nucleotide polymorphism and ultrasound imaging characteristics:In FBC group,at rs799906 loci,the frequency of TC genotype was significantly higher than other two genotypes in patients with microcalcification(P < 0.05).CC genotype showed higher incidence of high echo halo sign(P<0.05).At the rs3757318 locus,the frequency of TC genotype was significantly higher than other two genotypes in patients with microcalcification(P < 0.05).AG genotype showed higher incidence of small calcification.At the rs2046210 locus,The frequency of the aspect ratio>1,microcalcification and spiculation was higher in TT genotype than two other genotypes at the rs2046210 locus.(P< 0.05).In SBC group,at rs799906 loci,the frequency of TC genotype was significantly higher than other two genotypes in patients with microcalcification(P < 0.05).At rs3757318 loci,the frequency of AG genotype was significantly higher than other two genotypes in patients with microcalcification(P < 0.05).At rs2046210 loci,the frequency of TT genotype was significantly higher than other two genotypes in patients with microcalcification(P < 0.05).(3)Compare the positive genotypes,we found that in patients with aspect ratio>1,the incidence of TT genotype at rs2046210 site was higher in FBC group than in SBC group.In patients with microcalcification,the incidence of TC genotype at rs799906 loci and TT genotype at rs2046210 loci were higher in FBC group than in SBC group,whereas AG genotype at rs3757318 loci was higher in SBC group.In patients with speculation,the incidence of TT genotype at rs2046210 loci was higher in FBC group than in SBC group.Among three high positive rate locus genotype,rs799906-TC Vmax in the FBC group was26.417±21.016,7.284±7.153 in the SBC group(P< 0.05);Rs2046210-TT in the FBC group 27.168 ± 7.133,7.271 ± 20.025 in the SBC group(P<0.05);Rs3757318-AG in Vmax showed no statistical difference between two groups.There was no significant difference in RI values between the three high positive rate loci.CONCLUSION(1)Compared with sporadic breast cancer,patients with familial breast cancer showed a more pronounced ultrasound,which means the tumor was more malignant.(2)BRCA1 and related susceptibility gene single nucleotide polymorphisms(SNPs)is related to the ultrasound imaging features of familial and sporadic breast cancer,patients with positive susceptibility gene showed large aspect ratio,more speculation and micro-calcification.(3)The incidence of rs2046210-TT?rs799906-TC was higher in familial breast cancer with malignant sign than in sporadic breast cancer,it may be the specific genotype of familial breast cancer,especially rs2046210-TT.The incidence of rs3757318-AG was higher in sporadic breast cancer with malignant sign than in familial breast cancer,and it may be the specific genotype of sporadic breast cancer.