实用肿瘤杂志2018，Vol.33Issue(2)：133-138,6.
中国家族性乳腺癌患者碱基切除修复基因MUTYH的胚系突变研究
Germline mutations of base excision repair gene MUTYH in Chinese familial breast cancer patients
摘要
Abstract
Objective To characterize the mutation pattern of MUTYH gene in Chinese BRCA1/2-negative women with familial breast cancer,and to investigate its association with the development of breast cancer.Methods Gene sequencing was used to screen the germline mutations of MUTYH in 90 cases of BRCA1/2-negative Chinese familial breast cancer patients.Genomic databases were investigated in combination with In silico analysis to classify the mutations.Meanwhile,250 sporadic breast cancer patients and 250 healthy women were included as the control.The association between gene mutation and the development of breast cancer was confirmed by case-control study.Results A total of six variants were found,including c.925-2A ＞ G,c.53C ＞ T (p.P18L),c.74G ＞ A (p.G25D),c.1005G ＞ C (p.Q335H),c.1576C ＞ A (p.L526M) and c.1422G ＞ C (p.T474T).The most common variant was c.1005G ＞ C,which has both heterozygous and homozygous mutations.The genotype frequencies of GG,GC and CC were 33.3％ (30/90),46.7％ (42/90) and 21.1％ (19/90),respectively.The other five variants were heterozygous.Besides,no significant difference was observed in the frequency of c.925-2A ＞ G or c.74G ＞ A between sporadic breast cancer patients and the healthy controls (P ＞ 0.05).Moreover,none of c.1576C ＞ A variant was detected in neither sporadic breast cancer patients nor healthy controls.The variant c.925-2A ＞ G had no linkage with cancer in the family.Conclusion The splice-site variant c.925-2 A ＞ G of MUTYH was not a pathogenic variant for breast cancer.Future research is warranted to test whether c.53C ＞T,c.1005G ＞ C and c.1576C ＞ A were related to familial breast cancer in China.关键词
乳腺肿瘤/遗传学/DNA修复/基因,BRCA1/基因,BRCA2/多态性,单核苷酸/寡核苷酸序列分析/突变/聚合酶链反应/中国Key words
breast neoplasms/genetics/DNA repair/genes, BRCA1/genes, BRCA2/polymorphism, single nucleotide/oligonucleotide array sequence analysis/mutation/polymerase chain reaction/China分类
医药卫生引用本文复制引用
曹文明,高赟,潘志文,王晓稼..中国家族性乳腺癌患者碱基切除修复基因MUTYH的胚系突变研究[J].实用肿瘤杂志,2018,33(2):133-138,6.基金项目
国家自然科学基金(81672597) （81672597）
浙江省自然科学基金(LY17H160038) （LY17H160038）
浙江省医药卫生科研基金(2014KYA006、2017RC014) （2014KYA006、2017RC014）
