CAJ | 학술논문

目的检测新疆地区维吾尔族(简称维族)和汉族妇女早发性乳腺癌患者乳腺癌易感基因1相互作用蛋白1(BACH1)基因外显子突变情况,探讨维、汉族共有的突变位点与临床病理特征的相关性.方法直接测序法检测新疆地区维吾尔族与汉族妇女早发性乳腺癌(年龄30 ～ 40岁,各80例)BACHI基因外显子区域的突变情况.结果 (1)维族、汉族共检测出4个共有的突变位点,包括2个错义突变、2个同义突变,分别位于外显子(EXON)6、EXON19和EXON20.Polyphen和SIFT软件预测蛋白质功能,结果表明维、汉早发性乳腺癌患者共有的突变位点rs4986764可能为有害突变,可能影响BACH1蛋白质的功能.(2)在汉族人群中,c.587A→G、rs4986765、rs49867654、rs4986763位点的野生型与突变型在三阴性、非三阴性乳腺癌中的差异均无统计学意义(P＞0.05).但rs49867654、rs4986763位点的野生型与突变型在组织学分级Ⅰ+Ⅱ、Ⅲ级中的差异有统计学意义(P＜0.05),与野生型基因型比较,突变型基因型可降低病理组织学分级[比值比(OR)=0.063、0.015].在维族人群中,上述3个位点的野生型与突变型在三阴性、非三阴性乳腺癌及组织学分级Ⅰ+Ⅱ、Ⅲ级中的差异均无统计学意义(P＞0.05).结论在汉族人群中,rs49867654、rs4986763位点的突变型基因型可降低病理组织学分级,但在维族人群中未见统计学差异.
목적 검측신강지구유오이족(간칭유족)화한족부녀조발성유선암환자유선암역감기인1상호작용단백1(BACH1)기인외현자돌변정황,탐토유、한족공유적돌변위점여림상병리특정적상관성.방법 직접측서법검측신강지구유오이족여한족부녀조발성유선암(년령30 ～ 40세,각80례)BACHI기인외현자구역적돌변정황.결과 (1)유족、한족공검측출4개공유적돌변위점,포괄2개착의돌변、2개동의돌변,분별위우외현자(EXON)6、EXON19화EXON20.Polyphen화SIFT연건예측단백질공능,결과표명유、한조발성유선암환자공유적돌변위점rs4986764가능위유해돌변,가능영향BACH1단백질적공능.(2)재한족인군중,c.587A→G、rs4986765、rs49867654、rs4986763위점적야생형여돌변형재삼음성、비삼음성유선암중적차이균무통계학의의(P＞0.05).단rs49867654、rs4986763위점적야생형여돌변형재조직학분급Ⅰ+Ⅱ、Ⅲ급중적차이유통계학의의(P＜0.05),여야생형기인형비교,돌변형기인형가강저병리조직학분급[비치비(OR)=0.063、0.015].재유족인군중,상술3개위점적야생형여돌변형재삼음성、비삼음성유선암급조직학분급Ⅰ+Ⅱ、Ⅲ급중적차이균무통계학의의(P＞0.05).결론 재한족인군중,rs49867654、rs4986763위점적돌변형기인형가강저병리조직학분급,단재유족인군중미견통계학차이.
Objective Detect the state of common mutation locus of breast cancer susceptibility gene 1 (BRCA1) associated C terminal helicase 1 (BACH1) gene in exon of the early onset breast cancer women patients of Uygur and Han nationalities in Xinjiang region and discuss the correlation between common mutation locus of Uygur and Han nationalities and clinicopathologic features.Methods Detect the state of mutation of BACH1 gene in exon of the early onset breast cancer women patients of Uygur and Han nationalities in Xinjiang region (aged 30-40, 80 cases each) by direct sequencing.Results 4 common mutation locus of Uygur and Han nationalities have been detected, including 2 missense mutations and 2 silent mutations, which are in the position of EXON6, EXON19 and EXON20 respectively.Predicting protein functions with Polyphen and SIFT softwares shows that among common mutation locus of the early onset breast cancer patients of Uygur and Han nationalities, the common mutation site rs4986764 is probably a detrimental mutation, which could affect the function of protein BACH1.Among Han nationality people, wild type and mutant type of locus c.587A→G, rs4986765, rs49867654, rs4986763 have no statistical significance in differences between triple-negative breast cancer and non-triple-negative breast cancer (P ＞ 0.05).While wild type and mutant type of locus rs49867654, rs4986763 do have statistical significance in differences between grade Ⅰ + Ⅱ and grade Ⅲ in histological grade (P ＜ 0.05).Compared with wild type gene, mutant gene can degrade pathologic histology-grading [odds ratio (OR) =0.063, 0.015], Among Uygur nationality people, wild type and mutant type of the three locus above have no statistical significance in triple-negative breast cancer, non-triple-negative breast cancer, grade Ⅰ + Ⅱ and grade Ⅲ in histological grade (P ＞ 0.05).Conclusion Mutant gene on locus rs49867654, rs4986763 can degrade pathologic histology-grading among Han nationality people, while there is no statistical significance among Uygur nationality people.