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Genomic Approaches to Identifying Breast Cancer Susceptibility Factors

机译：识别乳腺癌易感性因素的基因组方法

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The majority of the genetic variants underlying susceptibility to breast cancer are yet to be discovered. Genome-wide linkage analyses, utilizing anonymous genetic markers, have been successful at identifying two genes, BRCA1 and BRCA2, which account for a sizeable fraction of the clearly inherited forms of breast cancer occurring in autosomal dominant Mendellian patterns. Mutations in these genes, however, account for less than ¼ of the total genetic component of breast cancer susceptibility and the remaining component is likely to be polygenic in nature - the interaction of mutations in multiple genes, each with a weak effect, in combination with environmental influences. The identification of these polygenes will likely require the study of large numbers of unrelated subjects with and without breast cancer in case-control association studies. Until the time when complete genome sequence information is feasible for all study subjects, interim strategies involving a subset of all common genetic variation (primarily single nucleotide polymorphisms, SNPs) are being planned. Assuming the common disease-common variant theory of complex disease susceptibility, studying a very dense set of genetic markers is likely to identify breast cancer susceptibility genes by virtue of including either the biologically relevant variant, or one closely correlated with it due to linkage disequilibrium.
机译：尚未发现对乳腺癌易感性的大多数遗传变异。利用匿名遗传标记的全基因组连锁分析已成功鉴定出两个基因BRCA1和BRCA2，这两个基因占以常染色体显性孟德尔模式发生的明显遗传形式的乳腺癌的很大一部分。但是，这些基因中的突变占乳腺癌易感性总遗传成分的不到1/4，而其余成分本质上很可能是多基因的-多个基因中的突变相互影响，而每个基因的相互作用较弱环境影响。这些多基因的鉴定可能需要在病例对照研究中研究大量有或没有乳腺癌的无关受试者。在所有研究对象都可获得完整的基因组序列信息之前，正在计划涉及所有常见遗传变异子集（主要是单核苷酸多态性，SNP）的临时策略。假设复杂疾病易感性的常见疾病-常见变异理论，研究非常密集的一组遗传标记很可能会通过包括生物学相关变异或由于连锁不平衡而与之密切相关的一个变异来识别乳腺癌易感基因。

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  • 来源
    《Breast Disease》 |2004年第1期|3-9|共7页
  • 作者

    Jeffery P. Struewing;

  • 作者单位

    Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-5060, USA;

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