Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4608, USA.
Hum Genet. 2011 Jul;130(1):59-78. doi: 10.1007/s00439-011-1030-9. Epub 2011 Jun 16.
Genome-wide association studies in cancer have already identified over 150 regions associated with two dozen specific cancers. Already, a handful of multi-cancer susceptibility regions have been uncovered, providing new insights into perhaps common mechanisms of carcinogenesis. For each new susceptibility allele, investigators now face the arduous task of interrogating each region beginning with fine mapping prior to pursuing the biological basis for the direct association of one or more variants. It appears that there may be a significant number of common alleles that contribute to the heritability of a specific cancer. Since each region confers a small contribution to the risk for cancer, it is daunting to consider any single nucleotide polymorphism (SNP) as a clinical test. Since the complex genomic architecture of each cancer differs, additional genotyping and sequence analysis will be required to comprehensively catalog susceptibility alleles followed by the formidable task of understanding the interactions between genetic regions as well as the environment. It will be critical to assess the applicability of genetic tests in specific clinical settings, such as when to perform screening tests with calculable risks (e.g., biopsies or chemoprevention), before incorporating SNPs into clinical practice. To advance the current genomic observations to the clinical venue, new studies will need to be designed to validate the utility of known genetic variants in assessing risk for cancer as well as its outcomes.
癌症的全基因组关联研究已经确定了超过 150 个与二十多种特定癌症相关的区域。已经发现了少数多个癌症易感性区域，为致癌发生的可能共同机制提供了新的见解。对于每个新的易感性等位基因，研究人员现在面临着艰巨的任务，即首先进行精细映射，然后在研究一个或多个变体的直接关联的生物学基础之前，对每个区域进行询问。似乎有相当数量的常见等位基因对特定癌症的遗传性有贡献。由于每个区域对癌症的风险仅产生微小的影响，因此考虑任何单个核苷酸多态性（SNP）作为临床检测都是令人生畏的。由于每个癌症的复杂基因组结构都不同，因此需要进行额外的基因分型和序列分析，以全面编目易感性等位基因，然后艰巨的任务是理解遗传区域以及环境之间的相互作用。评估遗传测试在特定临床环境中的适用性至关重要，例如在何时进行具有可计算风险的筛查测试（例如活检或化学预防），然后将 SNPs 纳入临床实践。为了将当前的基因组观察结果推进到临床领域，需要设计新的研究来验证已知遗传变异在评估癌症风险及其结果方面的效用。
