| Objective:In this study,polymorphism analysis of ataxia-telangiectasia mutated gene(ATM)rs 189037 and rs609261 were detected and analyzed in breast specimens,explore the correlation between allele and gene frequency of two loci and genetic susceptibility and clinicopathological characteristics of breast cancer.This study enriches the pathogenesis of breast cancer and provides important basis and ideas for early diagnosis preventive intervention,treatment and prognostic evaluation of breast cancer.Methods:This study collected tissue samples from patients with breast cancer and benign breast tumors confirmed by pathology in the Fourth Affiliated Hospital of Guangxi Medical University.There were 150 cases of breast cancer at rs 189037 and 141 cases of the control group(benign bteast tumor group),128 cases of breast cancer at rs609261 and 143 cases of the control group(benign bteast tumor group).At the same time,medical records were consulted to collect the clinical information of the patients,including age,tumor,site,tumor size,lymph node metastasis and immunohistochemical indicators:estrogen receptor(ER),progestrone receptor(PR),HER-2,Ki-67.The polymorphism of ATM gene at rs 189037 and rs609261was analyzed by multiple SnaPshot method,the samples were verified by first generation sequencing(Sanger method).The distribution frequency of genotypes and alleles were calculated.The hardy-Weinberg Equilibrium(HWE)of the two points was detected by using the goodness-of-fit χ 2.After correcting the age and gender by binary Logistic regression analysis,Compare Odds ratio(OR)and 95%Confidential Interval(CI).To analyze the relationship between Single nucleotide polymorphism(SNP)of two SNPs and genetic susceptibility and clinicopathological characterstics of breast cancer.Results:1.Genotype distribution of ATM gene rs 189037 in 150 cases of breast cancer group and 141 cases of control group conforms to Hardy-weinberg equilibrium(P>0.05);genotype distribution of ATM gene rs609261 in 128 cases of breast cancer group and 143 cases of control group conforms to Hardy-weinberg equilibrium(P>0.05).2.Comparison of genotype and allele frequency of ATM gene rs189037 and rs609261 in each group.(1)There were three genotypes of rs189037:GG、GA and AA,the genotype frequency of breast cancer group was GG(32%),GA(52.7%),AA(15.3%),and those of control group was GG(33.3%),GA(55.4%),AA(11.3%).There was no statistical difference in genotype distribution between the two groups(P>0.05).The distribution frequency of G allele in breast cancer group and control group was 58.3%and 61.0%,the A allele frequency of breast cancer group and control group was 41.7%and 39.0%.There was no significant difference in allele distribution between the two groups(P>0.05).Hybrid model(GA VS GG),homozygous model(AA VS GG),(A)VS G allele model,the dominant model(GA+AA VS GG)and implicit model(AA VS GA+GG)in the breast cancer group and the control group,no correlation(P>0.05).(2)There were TT,TC and CC genotypes at rs609261.The genotype frequencies of the breast cancer group were TT(34.4%),TC(51.6%)and CC(14.0%),while those of the control group were TT(37.8%),TC(53.1%)and CC(9.1%).There was no statistical difference in genotype distribution between the two groups(P>0.05).The frequency of T allele was 60.2%and 64.3%in the breast cancer group and the control group,and the frequency of C allele was 39.8%and 35.7%in the breast cancer group and the control group,respectively.There was no statistical difference in the distribution of allele between the two groups(P>0.05).Hybrid model(TC VS TT),homozygous model(CC VS TT),(C v T),the dominant allele model model(TC+CC VS TT)and implicit model(CC vs.TC+TT)in breast cancer group and the control group,and the risk of no correlation(P>0.05).3.Age stratification analysis of genetic mutation of ATM gen se 18903 7 and rs609261 and genetic susceptibility to breast cancer.(1)Age stratification analysis of genetic mutation at ATM gene rs 189037 and genetic susceptibility to breast cancer in age groups≥51 years old.In age groups≥51 years old,there were 76 cases in the breast cancer group and 19 cases in the control group.There was no significant difference in allele distribution frequency between breast cancer group and control group(P>0.05).Hybrid model(GA VS GG),homozygous model(AA VS GG),(A)VS G allele model,the dominant model(GA+AA VS GG)and implicit model(AA VS GA+GG)in the breast cancer group and the control group,no correlation(P>0.05).(2)Age stratification analysis of genetic mutation at ATM gene rs 189037 and genetic susceptibility to breast cancer in age groups<51 years old.In age groups<51 years old,there were 74 cases in the breast cancer group and 122 cases in the control group.There was no significant difference in allele distribution frequency between breast cancer group and control group(P>0.05).Hybrid model(GA VS GG),homozygous model(AA VS GG),(A)VS G allele model,the dominant model(GA+AA VS GG)and implicit model(AA VS GA+GG)in the breast cancer group and the control group,no correlation(P>0.05).(3)Age stratification analysis of genetic mutation at ATM gene rs609261and genetic susceptibility to breast cancer in age groups≥51 years old.In age groups≥51 years old,there were 63 cases in the breast cancer group and 19 cases in the control group.There was no significant difference in allele distribution frequency between breast cancer group and control group(P>0.05).Hybrid model(TC VS TT),homozygous model(CC VS TT),(C v T),the dominant allele model model(TC+CC VS TT)and implicit model(CC vs.TC+TT)in breast cancer group and the control group,and the risk of no correlation(P>0.05).(4)Age stratification analysis of genetic mutation at ATM gene rs609261 and genetic susceptibility to breast cancer in age groups<51 years old.In age groups<51 years old,there were 65 cases in the breast cancer group and 124 cases in the control group.There was no significant difference in allele distribution frequency between breast cancer group and control group(P>0.05).Hybrid model(TC VS TT),homozygous model(CC VS TT),(C v T),the dominant allele model model(TC+CC VS TT)and implicit model(CC vs.TC+TT)in breast cancer group and the control group,and the risk of no correlation(P>0.05).4.The relationship of ATM gene rs 189037 and rs609261 loci with clinicopathological features of breast cancer:(1)Among ATM gene rs 18903 7 locus,there were 150 breast cancer patients,74 patients were less than 51years old,and 76 patients were more than 51years old;72 left breast patients and 78 right breast patients;20 cases of other types and 130 cases of invasive ductal carcinoma.There were 34 patients with tumor size greater than or equal to 5cm,and 116 patients with tumor size less than 5cm.There were 68 patients with metastasis and 82 patients without lymph node metastasis.The polymorphism of ATM gene rs 189037 was not correlated with location,the age,tumor size,pathological type and lymph node metastasis of breast cancer(P>0.05).(2)Among ATM gene rs609261 locus,there were 128 breast cancer patients,65 patients were less than 51 years old,and 63 patients were more than 51 years old;63 left breast patients and 65 right breast patients;18 cases of other types and 110 cases of invasive ductal carcinoma.There were 28 patients with tumor size greater than or equal to 5cm,and 100 patients with tumor size less than 5cm.The polymorphism of ATM gene rs609261 was not correlated with location,the age,tumor size,pathological type of breast cancer(P>0.05).There were60 patients with metastasisand 68 patients with no lymph node metastasis.Logistic regression analysis showed that patients with TC and CC genotypes had a significantly increased risk of lymph node metastasis compared with TT genotypes(OR=2.587,95%CI:1.202-5.568).5.Difference of genotype and allele frequency of ATM gene rs189037and rs609261 in immunohistochemical indexes:(1)Among ATM gene rs189037 locus,there were 150 breast cancer patients,112estrogen receptor(ER)positive patients and 38 negative patients;There were 96 positive progesterone receptor(PR)patients and 54 negative;There were 119 positive and 31 negative human epidermal growth factor receptor 2(HER-2)patients;There were 115 patients with high expression and 35 patients with low expression of Ki-67.There was no correlation between the polymorphism of ATM gene rs 189037 and the expression of ER,PR,HER-2 and Ki-67 in breast cancer(P>0.05).(2)Among the ATM gene rs609261 loci,there were 128 breast cancer patients,93 ER positive patients and 35 negative patients.There were80 patients and 48 patients with negative PR with positive PR;There were 105 patients with positive HER-2 and 23 patients with negative HER-2.There were97 patients with high expression and 31 patients with low expression of Ki-67.There was no correlation between the polymorphism of ATM gene rs609261 and the expression of ER,PR,HER-2 and Ki-67 in breast cancer(P>0.05).Conclusion:1.There was no significant correlation between ATM gene rs 189037 and rs609261 gene polymorphism and the risk of breast cancer.2.There was no correlation between ATM gene rs 189037 and rs609261 mutation and age stratification of genetic susceptibility to breast cancer.3.There was no correlation between the genotype and allele frequency of ATM gene rs 189037 and their clinicopathological characteristics.In rs609261 locus,patients with TC and CC genotypes were found to be associated with lymph node metastasis.4.There was no correlation between genotype and allele frequency of ATM gene rs 189037 and rs609261 and the immunohistochemical indexes. |
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