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The Association Of Type2Diabetes Susceptibility Genetcf7l2, Igf2bp2Polymorphism And The Risk Of Breast Cancer In Chinese Han Female

Posted on:2015-01-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:G H LiuFull Text:PDF
GTID:1264330428474017Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Breast cancer is one of the most common malignant tumors in females.With an annual incidence rate increased by more than3%in the past few years,it is the number one cause in morbidity among all the malignant tumor typesin Chinese females. Diabetes, often referred to as diabetes mellitus, is a groupof diseases characterized by glycometabolism disorders and caused by geneticas well as environmental reasons. Insulin deficiency and dysfunction may acttogether or independently to induce metabolic disorders of carbohydrates,lipids, proteins, water and electrolytes. There have recently been drasticincreases in the incidence rate of diabetes in a worldwide range, and China isbecoming one of the countries with the highest diabetes morbidity, where thediabetes population is expected to exceed that of India and become No.1in2020. There is Meta analysis that shows the corresponding risk of breastcancer in patients diagnosed with type2diabetes is1.2-1.5fold of that of thenormal people. In the first part of this research, to investigate the effects oftype2diabetes mellitus on the clinico-pathological characteristics andprognosis of breast cancer, we retrospectively analyzed the medical records of80breast cancer patients with type2diabetes and160non-diabetic breastcancer patients.More and more previous investigations indicate that there might becomplicated correlations between type2diabetes and breast cancers, but theunderlying mechanism remains to be explored. Gene mutations are believed tobe correlated with both of the above two diseases, and similar gene mutationsmight partially explain the correlation between diabetes and breast cancer. Thetranscription factor7-like2(TCF7L2) gene is located on the chromosome10q25.2, which was also known previously as TCF-4. The gene encodes ahigh mobility group box-containing transcription factor which is involved in Wnt/β-catenin signaling pathway. The analysis of multiple whole genomeassociation illustrates that TCF7L2is one of the susceptibility genes for type2diabetes. Barbara et al. investigated the effect of the TCF7L2rs12255372variant on familial breast cancer (BC) risk by means of TaqMan allelicdiscrimination. Their results suggest a possible influence of TCF7L2rs12255372on the risk of familial BC. Genotyping of TCF7L2polymorphisms was performed on387breast cancer patients and252healthywomen who had no history of any malignancy using polymerase chainreaction–restriction fragment length polymorphism (PCR–RFLP) method in ahospital-based Malaysian population by Naidu et al. The allele frequency ofrs7903146(T) polymorphism was significantly higher in the cancer patientsthan normal individuals. No significant association was demonstrated betweenCT and TT genotype and breast cancer risk. However, women who werecarriers of T allele or T allele genotype showed significant increased risk ofbreast cancer. The rs7903146(T) allele genotype was significantly associatedwith nodal involvement but rs12255372(T) allele genotype was not associatedwith the clinico-pathologic characteristics. In conclusion, rs7903146(T)variant may elevate the risk of breast cancer, thus could be a potentialcandidate for breast cancer susceptibility. The variant may also increase themetastatic potential of the tumor. The second part of this study is to investigatethe association of TCF7L2and the risk of breast cancer. The results showedthat the gene TCF7L2rs7903146, rs12255372polymorphisms were notassociated with the risk of breast cancer in Chinese Han. Many studies haveshown that the SNPs rs1470579and rs4402960in the second intron ofIGF2BP2gene is of medium risk in the development of type2diabetesmellitus, and such results have been proven by investigations and Metaanalysis repeated in various populations. However, there have not been anyreports about the correlations between IGF2BP2gene polymorphism andbreast cancer, and therefore we investigated the polymorphism of IGF2BP2gene, rs4402960, and its correlation to the risk of breast cancer in Chinesefemales of Han nationality. The research contents and results are as follows: Part I The clinico-pathologic characteristics and prognosis in breastcancer patients with type2diabetesObjective: To investigate the association of type2diabetes mellitus onthe clinico-pathologic characteristics and prognosis of breast cancer.Methods: A case-control study, which includes240female breast cancerPatients, who were in-hospital in the fourth affiliated hospital of HebeiMedical University from January2011to January2012. The Patients weredivided into two groups according to incidence of type2diabetes. Breastcancer and diabetes group included80patients, non-diabetic group included160patients. They all had been operated and their pathology slices werediagnosed primary breast. We reviewed patients’ medical records, includingpatient name, age, height, weight, blood glucose, age at menarche, parity,menopausal status, tumor size, lymph node metastasis, the major indexesimmunohistochemistry (ER, PR, HER-2, Ki-67), tumor histological grade,clinical stage and molecular typing, etc. SPSS13.0statistical software wasused to do the statistics analysis. Measurement data were expressed as mean standard deviation, and compared using t-test; count data tables were analyzedby the x2test. P <0.05was considered significantly difference.Results:1. Breast cancer patients with type2diabetes were older thanthose in non-diabetic group, the difference was statistically significant, butthere was no significant difference in BMI between the two groups.2. In breast cancer patients with type2diabetes, blood glucose weresignificantly higher than the non-diabetic patients, the difference wasstatistically significant.3. There were no significant difference in age at menarche and paritybetween Breast cancer patients with type2diabetes mellitus and non-diabeticpatients, postmenopausal patients in the group of breast cancer patients withtype2diabetes have significantly more than those in non-diabetic patientsgroup, there were significant differences between the two groups.4. There was no significant difference in the distribution of tumor size,lymph node metastasis, ER, PR, HER-2and Ki-67status between group of breast cancer patients with type2diabetes and non-diabetic group.5. Significant differences in the distribution of clinical stage, histologicalgrade and molecular typing between group of breast cancer patients with type2diabetes and non-diabetic group, the higher clinical stage, histological gradeand Basal-like type were found in group of breast cancer patients with type2diabetes than in non-diabetic group. The difference was statisticallysignificant.Conclusions:1. Breast cancer with type2diabetes is more common inpatients with older age and post menopause. Elder type2diabetes patientsespecially for postmenopausal should be regularly examined by breastultrasound and mammography.2. There was no significant difference in the distribution of BMI, age atmenarche, parity, tumor size, lymph node metastasis, ER, PR, HER-2andKi-67status between group of breast cancer patients with type2diabetes andnon-diabetic group. The higher clinical stage, histological grade and Basal-liketype were found in group of breast cancer patients with type2diabetes than innon-diabetic group. Type2diabetes is the risk factor of breast cancer withpoor prognosis. Female breast cancer patients with type2diabetes have laterclinical stage and poor prognosis.Part II The association of TCF7L2gene polymorphism with breast cancerrisk in Chinese Han femaleObjective: To investigate the relationship of nuclear transcription factor7like2(TCF7L2) gene which is one of diabetes susceptibility genespolymorphism and risk of breast cancer.Methods: In this case-control study, peripheral blood was extracted fromwomen with breast cancer hospitalized in The Fourth Hospital of HebeiMedical University and from the same period healthy volunteers in BethuneInternational Peace Hospital. Genomic DNA was extracted from peripheralblood. The TCF7L2rs7903146, rs12255372polymorphism were detected byPolymerase chain reaction-ligase detection reaction (PCR-LDR) method, andwe analyzed the relationships of genotype frequency distributions and the risk and clinic-pathological features of breast cancer. Statistical analysis wasperformed using SPSS13.0software package. Hardy–Weinberg analysis wasperformed by comparing the genotype frequencies in the control group usingthe chi-square test. The age and BMI difference of two groups was analyzedby the t-test. Comparison of the TCF7L2genotype and allele distribution inpatients and healthy controls was performed by Chi-square test. The odds ratio(OR) and95%confidence Interval (CI) were calculated using anunconditional logistic regression model. We assessed the relationship betweenTCF7L2single nucleotide polymorphisms and the risk of breast cancer andclinic-pathological parameters adjusted by age and BMI. P <0.05wasconsidered significantly difference.Results:1.The average age of breast cancer patients was49.1±9.6yearsand48.1±9.9years in the control group of patients. The difference was notstatistically significant. The body mass index was25.5±3.6kg/m2in breastcancer patients and25.4±3.5kg/m2in normal control group, the differencebetween the two groups was statistically significant (P <0.001).2. Two groups were not detected TT genotype.The genotype frequenciesof the TCF7L2rs7903146CC and CT in patients with breast cancer andcontrols were92.7%,7.3%and89.3%,10.7%respectively. No statisticallysignificant difference in the TCF7L2genotype distribution was demonstratedbetween cases and controls (χ2=3.369P=0.066). Compared to the CCgenotype, the CT genotype did not increase the risk of developing breastcancer, the odds ratio were1.522(95%CI=0.97-2.389). The allele frequenciesof the TCF7L2rs12255372CC and CT in patients with breast cancer andcontrols were98.2%,1.8%and97.7%,2.3%respectively. No statisticallysignificant difference in the TCF7L2allele distribution was demonstratedbetween cases and controls (χ2=0.312P=0.577). Compared to the CCgenotype, the CT genotype did not increase the risk of developing breastcancer, the odds ratio were1.295(95%CI=0.512-3.217).3. Stratified analysis by age at diagnosis found that the total number ofage at diagnosis <50years was301in breast cancer patients, of which there were14cases of rs7903146CT type. The mutation rate was4.7%. There were3cases of rs12255372GT type in301cases. The mutation rate was1%.Thetotal number of age at diagnosis≥50years was263in breast cancer patients,of which there were27cases of rs7903146CT type. The mutation rate was9.3%. There were7cases of rs12255372GT type in263cases. The mutationrate was2.7%. The mutation rate of TCF7L2rs7903146was significantlyhigher in breast cancer patients whose age at diagnosis≥50years than thoseage at diagnosis <50years. The difference of genotype between the twogroups was statistically significant (P <0.05), the odds ratio were2.345(95%CI=1.202-4.575). The difference of rs12255372mutation rate between twogroups was not statistically significant (P>0.05).4. Stratified analysis by menopausal status found that the total number ofpre-menopausal breast cancer patients was258, of which there were12casesof rs7903146CT type. The mutation rate was4.7%. The total number ofpost-menopausal breast cancer patients was278, of which there are26casesof CT type. The difference of genotype between the two groups wasstatistically significant (P<0.05). The rs7903146mutation rate inpostmenopausal breast cancer patients than those in pre-menopausal breastcancer patients, the odds ratio were2.115(95%CI=1.044-4.286). There were12cases of rs7903146CT type. The mutation rate was4.7%. There were onecases of GT type in pre-menopausal breast cancer patients. The mutation ratewas0.4%. There were seven cases of GT type in post-menopausal breastcancer patients. The mutation rate was2.5%. The difference in genotypedistribution between the two groups was not statistically significant (P>0.05).5. Stratified analysis by ER status showed that the total number of ERnegative breast cancer patients was179, of which there were12cases ofrs7903146CT type. The mutation rate was5.6%. There were two cases ofrs12255372GT type in179cases. The mutation rate was1.1%.The totalnumber of ER positive breast cancer patients was345, of which there are29cases of rs7903146CT type. The mutation rate was8.4%. There were eightcases of rs12255372GT type in345cases. The mutation rate was2.3%. The difference in genotype distribution between the two groups was notstatistically significant (P>0.05).6. Stratified analysis by PR status showed that the total number of PRnegative breast cancer patients was227, of which there were17cases ofrs7903146CT type. The mutation rate was7.5%. There were five cases ofrs12255372GT type in227cases. The mutation rate was2.2%.The totalnumber of PR positive breast cancer patients was296, of which there are22cases of rs7903146CT type. The mutation rate was7.4%. There were fivecases of rs12255372GT type in296cases. The mutation rate was1.7%. Thedifference in genotype distribution between the two groups was notstatistically significant (P>0.05).7. Stratified analysis by HER-2status showed that the total number ofHER-2negative breast cancer patients was396, of which there were27casesof rs7903146CT type. The mutation rate was6.8%. There were eight cases ofrs12255372GT type in227cases. The mutation rate was2%.The total numberof HER-2positive breast cancer patients was123of which there are11casesof rs7903146CT type. The mutation rate was8.9%. There were two cases ofrs12255372GT type in123cases. The mutation rate was1.6%. The differencein genotype distribution between the two groups was not statisticallysignificant (P>0.05).8. Stratified analysis by P53status showed that the total number of P53negative breast cancer patients was118, of which there were nine cases ofrs7903146CT type. The mutation rate was7.6%. There were three cases ofrs12255372GT type in118cases. The mutation rate was2.5%.The totalnumber of P53positive breast cancer patients was327, of which there are26cases of rs7903146CT type. The mutation rate was8%. There were four casesof rs12255372GT type in327cases. The mutation rate was1.2%. Thedifference in genotype distribution between the two groups was notstatistically significant (P>0.05).9. Stratified analysis by Ki-67status showed that the total number ofKi-67negative breast cancer patients was84, of which there were five cases of rs7903146CT type. The mutation rate was6%. There were one cases ofrs12255372GT type in84cases. The mutation rate was1.2%.The totalnumber of Ki-67positive breast cancer patients was463, of which there are30cases of rs7903146CT type. The mutation rate was7.9%. There were sixcases of rs12255372GT type in379cases. The mutation rate was1.6%. Thedifference in genotype distribution between the two groups was notstatistically significant (P>0.05).10. Stratified analysis by lymph node metastasis showed that the totalnumber of breast cancer patients without lymph node metastasis was251, ofwhich there were16cases of rs7903146CT type. The mutation rate was6.4%.There were five cases of rs12255372GT type in251cases. The mutation ratewas2%.The total number of breast cancer patients with lymph nodemetastasis was255, of which there are20cases of rs7903146CT type. Themutation rate was7.8%. There were three cases of rs12255372GT type in255cases. The mutation rate was1.2%. The difference in genotype distributionbetween the two groups was not statistically significant (P>0.05).11. Stratified analysis by tumor size showed that the total number ofbreast cancer patients whose tumor diameter≤2cm was248, of which therewere14cases of rs7903146CT type. The mutation rate was5.6%. There were1cases of rs12255372GT type in248cases. The mutation rate was0.4%.Thetotal number of breast cancer patients whose tumor diameter>2cm was234,of which there are20cases of rs7903146CT type. The mutation rate was8.5%. There were six cases of rs12255372GT type in234cases. The mutationrate was2.5%. The difference in genotype distribution between the two groupswas not statistically significant (P>0.05).12. Stratified analysis by histological grade showed that the total numberof histological grade of Ⅰ-Ⅱ breast cancer patients was349, of which therewere29cases of rs7903146CT type. The mutation rate was8.3%. There wereseven cases of rs12255372GT type in349cases. The mutation rate was7%.The total number of histological grade of Ⅲ breast cancer patients was46, of which there are1cases of rs7903146CT type. The mutation rate was 2.2%. There were zero cases of rs12255372GT type in234cases. Thedifference in genotype distribution between the two groups was notstatistically significant (P>0.05).13. Stratified analysis by tumor clinical staging showed that the totalnumber of stage Ⅰ breast cancer patients was155, of which there were ninecases of rs7903146CT type. The mutation rate was5.8%. There were twocases of rs12255372GT type in155cases. The mutation rate was1.3%.Thetotal number of stage Ⅱ breast cancer patients was215, of which there are19cases of rs7903146CT type. The mutation rate was8.8%. There were fivecases of rs12255372GT type in215cases. The mutation rate was2.3%. Thetotal number of stage Ⅲ breast cancer patients was156, of which there are10cases of rs7903146CT type. The mutation rate was6.4%. There were twocases of rs12255372GT type in156cases. The mutation rate was1.3%. Thetotal number of stage Ⅳbreast cancer patients was38, of which there arethree cases of rs7903146CT type. The mutation rate was7.9%. There wereone cases of rs12255372GT type in38cases. The mutation rate was2.6%.The difference in genotype distribution between the two groups was notstatistically significant (P>0.05).14. Stratified analysis by molecular typing showed that the total numberof Luminal A type breast cancer patients was74, of which there were fivecases of rs7903146CT type. The mutation rate was6.8%. There were onecases of rs12255372GT type in74cases. The mutation rate was1.4%.Thetotal number of Luminal B type breast cancer patients was254, of which thereare24cases of rs7903146CT type. The mutation rate was9.4%. There weresix cases of rs12255372GT type in254cases. The mutation rate was2.4%.The total number of ERBB2+type breast cancer patients was66, of whichthere are two cases of rs7903146CT type. The mutation rate was3%. Therewere zero cases of rs12255372GT type in66cases. The mutation rate was0%.The total number of Basal-like type breast cancer patients was93, of whichthere are six cases of rs7903146CT type. The mutation rate was6.5%. Therewere two cases of rs12255372GT type in38cases. The mutation rate was 2.2%. The difference in genotype distribution between the two groups was notstatistically significant (P>0.05).Conclusions:1.There was no significant difference between the age ofbreast cancer patients and normal control cases. BMI of breast cancer patientswas higher than which of the control cases, suggesting that BMI is a riskfactor for breast cancer disease. Normal people should pay attention to dietand exercise to decline BMI, thereby reducing the risk of breast cancer.2. The mutation of TCF7L2gene rs7903146polymorphisms in thepost-menopausal and age at diagnosis≥50years patients was significantlyhigher than the pre-menopause and age at diagnosis <50years patients. Themutation of TCF7L2gene rs12255372polymorphisms was not associatedwith menopausal status and age at diagnosis.3. There was no relationship between the TCF7L2gene rs7903146andrs12255372polymorphisms and risk of breast cancer, lymph node metastasis,estrogen receptor, progesterone receptor, HER-2receptor status, P53, Ki-67status, tumor size, histological grade, tumor stage and molecular typing.Part III The association of IGF2BP2gene polymorphism with breastcancer risk in Chinese Han femaleObjective: To investigate the relationship of Insulin-like growth factor2mRNA binding protein2(IGF2BP2) which is one of the diabetessusceptibility genes polymorphism and risk of breast cancer.Methods: In this case-control study, peripheral blood was extracted fromwomen with breast cancer hospitalized in The Fourth Hospital of HebeiMedical University and from the same period healthy volunteers in BethuneInternational Peace Hospital. Genomic DNA was extracted from peripheralblood. The IGF2BP2rs4402960polymorphism was detected by Polymerasechain reaction-ligase detection reaction (PCR-LDR) method, and we analyzedthe relationships of genotype frequency distributions and the risk andclinic-pathological features of breast cancer. Statistical analysis wasperformed using SPSS13.0software package. Hardy–Weinberg analysis wasperformed by comparing the genotype frequencies in the control group using the chi-square test. The age and BMI difference of two groups was analyzedby the t-test. Comparison of the IGF2BP2genotype and allele distribution inpatients and healthy controls was performed by Chi-square test. The odds ratio(OR) and95%confidence Interval (CI) were calculated using anunconditional logistic regression model. We assessed the relationship betweenIGF2BP2single nucleotide polymorphisms and the risk of breast cancer andclinic-pathological parameters and adjusted by age and BMI. p<0.05wasconsidered significantly difference.Results:1.The average age of breast cancer patients was49.1±9.6yearsand48.1±9.9years in the control group of patients. The difference was notstatistically significant. The body mass index was25.5±3.6kg/m2in breastcancer patients and25.4±3.5kg/m2in normal control group, the differencebetween the two groups was statistically significant (P <0.001).2. The frequencies of GT (43.3%), TT (6.2%), T genotype (GT+TT)(49.5%), and T allele (27.8%) were higher in cancer patients than thefrequencies of GT (36.5%), TT (3.6%), T genotype (40.1%), and T allele(21.8%) in the control groups. Women who were GT heterozygote (ORadj=1.442;95%CI,1.097-1.895) or TT homozygote (ORadj=2.0;95%CI,1.041–3.843), and carriers of T genotype (ORadj=1.494;95%CI,1.146–1.947)or T allele (ORadj=1.391;95%CI,1.120-1.727) were significantly associatedwith breast cancer risk.3. Stratified analysis by age at diagnosis found that the total number ofage at diagnosis <50years was301in breast cancer patients, of which therewere134cases of rs4402960GT type,16cases of rs4402960TT type and150cases of rs4402960T genotype. The mutation rate was44.5%,5.3%and49.8%, respectively. The total number of age at diagnosis≥50years was263in breast cancer patients, of which there were110cases of rs4402960GT type,19cases of rs4402960TT type and129cases of rs4402960T genotype. Themutation rate was41.8%,7.2%and49%, respectively. The difference ofrs4402960mutation rate between two groups was not statistically significant(P>0.05). 4. Stratified analysis by menopausal status found that the total number ofpre-menopausal breast cancer patients was258, of which there were134casesof rs4402960GT type,12cases of rs4402960TT type and124cases ofrs4402960T allele genotype. The mutation rate was43.4%,4.7%and48.1%,respectively. The total number of post-menopausal breast cancer patients was278, of which there121cases of rs4402960GT type,21cases of rs4402960TT type and142cases of rs4402960T genotype. The mutation rate was43.5%,7.6%and51.1%, respectively. The difference of genotype distributionbetween the two groups was not statistically significant (P>0.05).5. Stratified analysis by ER status showed that the total number of ERnegative breast cancer patients was179, of which there were71cases ofrs4402960GT type,11cases of rs4402960TT type and82cases of rs4402960T allele genotype. The mutation rate was39.7%,6.1%and45.8%, respectively.The total number of ER positive breast cancer patients was345, of whichthere were150cases of rs4402960GT type,20cases of rs4402960TT typeand170cases of rs4402960T genotype. The mutation rate was43.5%,5.8%and49.3%, respectively. The difference of genotype distribution between thetwo groups was not statistically significant (P>0.05).6. Stratified analysis by PR status showed that the total number of PRnegative breast cancer patients was227, of which there were92cases ofrs4402960GT type,14cases of rs4402960TT type and106cases ofrs4402960T allele genotype. The mutation rate was40.5%,6.2%and46.7%,respectively. The total number of PR positive breast cancer patients was296,of which there were128cases of rs4402960GT type,17cases of rs4402960TT type and145cases of rs4402960T genotype. The mutation rate was43.2%,5.7%and49%, respectively. The difference of genotype distribution betweenthe two groups was not statistically significant (P>0.05).7. Stratified analysis by HER-2status showed that the total number ofHER-2negative breast cancer patients was396, of which there were161casesof rs4402960GT type,26cases of rs4402960TT type and187cases ofrs4402960T genotype. The mutation rate was40.7%,6.6%and47.2%, respectively. The total number of HER-2positive breast cancer patients was123, of which there were59cases of rs4402960GT type,4cases of rs4402960TT type and63cases of rs4402960T genotype. The mutation rate was48%,3.3%and51.2%, respectively. The difference of genotype distributionbetween the two groups was not statistically significant (P>0.05).8.Stratified analysis by P53status showed that the total number of P53negative breast cancer patients was118, of which there were48cases ofrs4402960GT type,5cases of rs4402960TT type and53cases of rs4402960T genotype. The mutation rate was40.7%,4.2%and44.9%, respectively. Thetotal number of P53positive breast cancer patients was327, of which therewere139cases of rs4402960GT type,20cases of rs4402960TT type and159cases of rs4402960T genotype. The mutation rate was42.5%,6.1%and48.6%, respectively. The difference of genotype distribution between the twogroups was not statistically significant (P>0.05).9. Stratified analysis by Ki-67status showed that the total number ofKi-67negative breast cancer patients was84, of which there were39cases ofrs4402960GT type,2cases of rs4402960TT type and41cases of rs4402960T genotype. The mutation rate was46.4%,2.4%and48.8%, respectively. Thetotal number of Ki-67positive breast cancer patients was379, of which therewere155cases of rs4402960GT type,24cases of rs4402960TT type and179cases of rs4402960T genotype. The mutation rate was40.9%,6.3%and47.2%, respectively. The difference of genotype distribution between the twogroups was not statistically significant (P>0.05).10. Stratified analysis by lymph node metastasis showed that the totalnumber of breast cancer patients without lymph node metastasis was251, ofwhich there were106cases of rs4402960GT type,17cases of rs4402960TTtype and123cases of rs4402960T genotype. The mutation rate was42.2%,6.8%and49%, respectively. The total number of breast cancer patients withlymph node metastasis was255, of which there were109cases of rs4402960GT type,15cases of rs4402960TT type and124cases of rs4402960Tgenotype. The mutation rate was42.7%,5.9%and48.6%, respectively. The difference of genotype distribution between the two groups was notstatistically significant (P>0.05).11. Stratified analysis by tumor size showed that the total number ofbreast cancer patients whose tumor diameter≤2cm was248, of which therewere100cases of rs4402960GT type,15cases of rs4402960TT type and115cases of rs4402960T genotype. The mutation rate was40.3%,6%and46.4%,respectively. The total number of breast cancer patients whose tumordiameter>2cm was234, of which there were111cases of rs4402960GT type,14cases of rs4402960TT type and125cases of rs4402960T genotype. Themutation rate was47.4%,6%and53.4%, respectively. The difference ofgenotype distribution between the two groups was not statistically significant(P>0.05).12. Stratified analysis by histological grade showed that the total numberof histological grade of Ⅰ-Ⅱ breast cancer patients was349, of which therewere141cases of rs4402960GT type,17cases of rs4402960TT type and158cases of rs4402960T genotype. The mutation rate was40.4%,4.9%and45.3%, respectively. The total number of histological grade of Ⅲ breastcancer patients was46, of which there were18cases of rs4402960GT type,5cases of rs4402960TT type and23cases of rs4402960T genotype. Themutation rate was39.1%,10.9%and50%, respectively. The difference ofgenotype distribution between the two groups was not statistically significant(P>0.05).13. Stratified analysis by tumor clinical staging showed that the totalnumber of stageⅠbreast cancer patients was155, of which there were60cases of rs4402960GT type,11cases of rs4402960TT type and71cases ofrs4402960T genotype. The mutation rate was38.7%,7.1%and45.8%,respectively. The total number of stage Ⅱ breast cancer patients was215, ofwhich there were88cases of rs4402960GT type,10cases of rs4402960TTtype and98cases of rs4402960T genotype. The mutation rate was40.9%,4.7%and45.6%, respectively. The total number of stage Ⅲ breast cancerpatients was156, of which there were76cases of rs4402960GT type,11 cases of rs4402960TT type and87cases of rs4402960T genotype. Themutation rate was48.7%,7.1%and55.8%, respectively. The total number ofstage Ⅳbreast cancer patients was38, of which there were20cases ofrs4402960GT type,3cases of rs4402960TT type and23cases of rs4402960T genotype. The mutation rate was52.6%,7.9%and60.5%, respectively. Thedifference of genotype distribution between the two groups was notstatistically significant (P>0.05).14. Stratified analysis by molecular typing showed that the total numberof Luminal A type breast cancer patients was74, of which there were33casesof rs4402960GT type,2cases of rs4402960TT type and35cases ofrs4402960T genotype. The mutation rate was44.6%,2.7%and47.3%,respectively. The total number of Luminal B type breast cancer patients was254, of which there were108cases of rs4402960GT type,16cases ofrs4402960TT type and124cases of rs4402960T genotype. The mutation ratewas42.5%,6.3%and48.8%, respectively. The total number of ERBB2+typebreast cancer patients was66, of which there were30cases of rs4402960GTtype,2cases of rs4402960TT type and32cases of rs4402960T genotype.The mutation rate was45.5%,3%and48.5%, respectively. The total numberof Basal-like type breast cancer patients was93, of which there were35casesof rs4402960GT type,6cases of rs4402960TT type and41cases ofrs4402960T genotype. The mutation rate was37.6%,6.5%and44.1%,respectively. The difference of genotype distribution between the two groupswas not statistically significant (P>0.05).Conclusions:1.There was no significant difference between the age ofbreast cancer patients and normal control cases. BMI of breast cancer patientswas higher than which of the control cases, suggesting that BMI is a riskfactor for breast cancer disease. Normal people should pay attention to dietand exercise to reduce BMI, thereby reducing the risk of breast cancer.2. There was significant relationship between the IGF2BP2geners4402960polymorphism and risk of breast cancer. The frequencies adjustedby age and BMI of T genotype (GT+TT)(ORadj=1.494,95%CI=1.146-1.947) and T allele (ORadj=1.391,95%CI=1.120-1.727) were significantlyincreased the risk of breast cancer. But there was no association betweenIGF2BP2gene rs4402960polymorphism and age at diagnosis, lymph nodemetastasis, estrogen receptor, progesterone receptor, HER-2receptor status,P53, Ki-67status, tumor size, histological grade, tumor clinical stage andmolecular typing.
Keywords/Search Tags:Breast cancer, type2diabetes, clinicopathological features, prognosis, polymorphism, TCF7L2, IGF2BP2
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