Mutation Analysis Of BRCA1-related BACH1?ZBRK1 Genes And Genetic Susceptibility Of Female Early-onset Breast Cancer Of Different Nationalities In XinJiang

Objective: To investigate the mutation differences of BACH1 ? ZBRK1 genes of early-onset in Han and Uygur nationality women in Xinjiang.Based on the selected mutation sites,we further analyzed the association between the single nucleotide polymorphisms?SNPs?of the above-mentioned genes and the genetic predisposition of breast cancer and the genetic pathogenic effects on breast cancer in different nationalities.Methods: Use DNA direct sequencing method to detect BACH1?ZBRK1gene exon sites respectively in 160 early-onset breast cancer cases??40 years?of Uygur and Han nationality women?80 cases for each nationality?.Find out the high frequency and functional sites.Then detecting genotype of these sites with the Snapshot genotyping technology on 480 healthy young women of Uygur and Han nationality?240 cases for each nationality?.Analyzed the relationship between different genotype distribution of two genes and risk of early-onset breast cancer in different nationalities by unconditional logistic regression model.Results:?1?There are differences on clinical pathological characteristics of early-onset breast cancer between two nationalities,and different ethnic groups have different risk factors for breast cancer.The number of parturition of 2 or more times,primary tumor 2-5 cm,axillary lymph node metastasis number 4-10,ER and PR negative rate were higher in Uygur patients than in Han patients,there was statistically significant difference between two groups?P < 0.05?.In comparison with healthy people,it was found that the family history of breast cancer in the first-degree relatives of the Han nationality was statistically significant between cases and healthy controls?P<0.05?.In the Uygur,the age of menarche and the age of first birth were statistically significant in the cases and healthy controls?P<0.05?.The family history ofbreast cancer?early age at first birth,early age at menarche may be risk factor for breast cancer.?2?Mutation sites of BACH1 and ZBRK1 gene are not the same between the Uygur and Han nationality women.Nine different mutation sites of BACH1 gene were detected in both Uygur and Han nationality breast cancer patients,the mutation frequency of rs4986764 in different ethnic groups was significantly different?P<0.05?.New mutations c.2990₂993del,c.2992₂995del,which been detected only in Han nationality breast cancer patients,are deletion mutations.SNP result showed,the frequencies of genotypes of mution rs4986764 showed significant differences between Han nationality breast cancer patients and Han nationality healthy control groups?P <0.05?,CC and TC+CC dominant model significantly reduced the risk of Han nationality breast cancer.Meanwhile,the interactions of TC+CC dominant model of mution rs4986764 and AG+GG dominant model of mution rs4986765 increased about 2.4 times risk of Han nationality breast cancer.The frequencies of genotypes of rs4986765 ?rs4986764 and MUTATION?c.587 A > G?of BACHI gene manifested differences between Uygur nationality breast cancer patients and Uygur nationality healthy control groups?P < 0.05?,TC ? CC and TC+CC dominant model of rs4986764 site both significantly reduced the risk of Uygur breast cancer,GG?AG+GG dominant model of rs4986765 site and GG,AG+GG dominant model of MUTATION?c.587A>G?site both significantly increased the risk of Uygur breast cancer.the interactions of TC+CC dominant model of mution rs4986764 and AG+GG dominant model of mution rs4986765 reduced 1.3%risk of Uygur breast cancer.?3?Eight different mutation sites of ZBRK1 gene were detected in both Uygur and Han nationality breast cancer patients,including 5 missense mutations.Protein function prediction result showed,the common mutation sites rs4987241 of Uygur and Han nationality and mutation sites rs2278415 only in Han nationality might be th detrimental mutations.SNP result showed,the frequencies of genotypes of mution rs4987241 showed no significant differences between Han nationality breast cancer patients and Han nationality healthy control groups?P >0.05?.There was no significant difference compare all the wild type and mutant type of both mutation sites with ER,PR?Her-2 expression?Histopathological grade on Han nationality breast cancer patients?P > 0.05?.There was also no significant difference between all the wild type and mutant type of both mutation sites and ER?PR?Her-2expression on Uygur breast cancer patients,the proportion of gradeIII wild type of mution rs2278415 was significantly lower than that of the mutant type?P<0.05?,the wild type and the mutant type of the rest mution sites showed no significant differencebetween gradeI^II and gradeIII?P>0.05?.Conclusion: The clinical and pathological features are different between Uygur and Han breast cancer patients,compared with Han,Uygur patients showed the later clinical stage and poor prognosis.SNP of rs4986764 of BACHl gene is associated with significantly reduces risk of early-onset breast cancer in Uygur and Han nationality women,SNP of rs4986765 is associated with significantly increases risk of breast cancer in Uygur women,SNP of MUTATION?c.587A>G?is associated with significantly increases risk of breast cancer in Uygur women.Mutations of ZNF350 gene are correlation with Uygur breast cancer,the mutation site rs2278415 may be genetic susceptibility loci on Uygur breast cancer.