Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population
Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population
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DOI：
10.1093/hmg/6.2.285
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发表时间：
1997-02-01
影响因子：
3.5
通讯作者：
Ponder, BAJ
中科院分区：
文献类型：
--
作者：
Dunning, AM;Chiano, M;Ponder, BAJ
大多数年轻发病的乳腺癌和卵巢癌的多病例家族被认为是由于易感基因BRCA 1和SRCA 2中的高度外显突变，然而，这些突变在人群中并不常见，并且它们可能仅占所有乳腺癌发病率的百分之几。原则上，更大比例的乳腺癌可能是由于赋予更适度个体风险的常见变异。BRCA 1基因中有几种常见的多态性可引起氨基酸替换。我们在大量的乳腺癌和卵巢癌病例和配对对照中检测了其中四种多态性的频率：Gln356Arg，Pro871Leu，Glu1038Gly和Ser1613Gly。由于强烈的连锁不平衡，这四个位点仅产生三种频率> 1.3%的单倍型。由等位基因Gln356Pro871 Glu1038Ser1613和Gln356Leu871 Gly1038Gly1613定义的两种最常见的单倍型的频率分别为0.57和0.32，并且这些频率在患者和对照组之间没有显著差异，因此BRCA 1基因的最常见多态性对乳腺癌或卵巢癌风险没有显著贡献，然而，我们的数据表明，Arg356等位基因可能有不同的基因型分布在乳腺癌患者从对照组（Arg356纯合子是更常见的对照组，P = 0.01），这表明它可能对乳腺癌的保护。如果这一发现能够得到证实，它可能会提供一个深入了解BRCA1蛋白的结构特征，这对它的功能很重要。
Most multiple case families of young onset breast cancer and ovarian cancer are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and SRCA2, However, these mutations are uncommon in the population and they probably account for only a few percent of all breast cancer incidence, A much larger fraction of breast cancer might, in principle, be due to common variants which confer more modest individual risks, There are several common polymorphisms in the BRCA1 gene which generate amino acid substitutions, We have examined the frequency of four of these polymorphisms: Gln356Arg, Pro871Leu, Glu1038Gly and Ser1613Gly in large series of breast and ovarian cancer cases and matched controls, Due to strong linkage disequilibrium, these four sites generate only three haplotypes with a frequency >1.3%. The two most common haplotypes, defined by the alleles Gln356Pro871 Glu1038Ser1613 and Gln356Leu871 Gly1038Gly1613, have frequencies of 0.57 and 0.32 respectively, and these frequencies do not differ significantly between patient and control groups, Thus the most common polymorphisms of the BRCA1 gene do not make a significant contribution to breast or ovarian cancer risk, However, our data suggest that the Arg356 allele may have a different genotype distribution in breast cancer patients from that in controls (Arg356 homozygotes are more frequent in the control groups, P = 0.01), indicating that it may be protective against breast cancer. If this finding can be confirmed, it may provide an insight into the structural features of the BRCA1 protein that are important for its function.