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首页> 外文期刊>Genetic testing and molecular biomarkers >The BRCA1 3'-UTR: 5711+421T/T_5711+1286T/T Genotype Is a Possible Breast and Ovarian Cancer Risk Factor
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The BRCA1 3'-UTR: 5711+421T/T_5711+1286T/T Genotype Is a Possible Breast and Ovarian Cancer Risk Factor

机译：BRCA1基因3’utr: 5711 + 421 T / T_5711 + 1286 T / T基因型可能是乳腺癌和卵巢癌风险因素

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摘要

A significant proportion of familial and early-onset breast and ovarian cancers occur in individuals without coding mutations of BRCA1 and BRCA2. Aims: We identified genetic variation at 3'-untranslated region (UTR) of BRCA1 in familial and early-onset breast and ovarian cancer patients both with and without BRCA1/2 mutation in the coding regions (BRCA1/2 pos and BRCA1/2 neg), and verified the possible cancer risk factor of the specific 31-UTR variation using functional analysis. Methods: BRCA1 SNP analysis was screened in 46 patients and 103 unaffected Thais by heteroduplex analysis and DNA sequencing. After chi-square test for the potential cancer association of the specific 3'-UTR genotypes, the functional tests were conducted using several strategies of the luciferase gene expression model. Results: We document the existence of two 3'-UTR polymorphic sites, the 5711+421(G or T) and the 5711+1286(C or T). Frequency of homozygous genotype 5711+421T/ T_5711+1286T/T (or T/T-T/T) in the group of BRCA1/2 neg cancer patients was triple of that seen in unaffected persons and showed a significant cancer association (p = 0.007). Functional analysis of these polymorphic sites using luciferase experiments showed an obvious significant reduction in activity associated with the T allele at both sites. Conclusion: These results suggest that the inheritance of specific 3'-UTR polymorphisms may predispose individuals to early-onset or familial breast or ovarian cancer.
机译：很大一部分的家族早发性乳腺癌和卵巢癌的发生个人没有编码的BRCA1突变和BRCA2。3 '非翻译区(UTR)家族的BRCA1和早发性乳腺癌和卵巢癌患者都没有BRCA1/2突变在编码区域(BRCA1/2 pos和BRCA1/2底片),验证可能的癌症风险因素的具体31-UTR变异使用功能分析。筛选病人46和103年不受影响吗泰国人通过heteroduplex分析和DNA测序。潜在的癌症协会的具体3’utr基因型,功能测试进行使用的几个策略荧光素酶基因表达模式。文档两个3’utr多态的存在网站,5711 + 421 (G和T)和5711 + 1286 (C或T)纯合基因型的频率5711 + 421 T / T_5711 + 1286 T / T(或T / T T / T)群BRCA1/2 neg癌症患者的三倍影响个人和显示重要的癌症协会(p = 0.007)。这些多态功能分析网站使用荧光素酶实验显示一个明显的显著减少活动联系在一起T等位基因在两个站点。结果表明,特定的继承3’utr多态性可能使个体早发性或家族性乳腺癌或卵巢癌癌症。

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