Center for Cancer Genomics, Wake Forest University, School of Medicine, Winston-Salem, NC 27157, USA.
J Intern Med. 2012 Apr;271(4):344-52. doi: 10.1111/j.1365-2796.2012.02522.x.
Genome-wide association studies have identified thousands of consistently replicated associations between genetic markers and complex disease risk, including cancers. Alone, these markers have limited utility in risk prediction; however, when several of these markers are used in combination, the predictive performance appears to be similar to that of many currently available clinical predictors. Despite this, there are divergent views regarding the clinical validity and utility of these genetic markers in risk prediction. There are valid concerns, thus providing a direction for new lines of research. Herein, we outline the debate and use the example of prostate cancer to highlight emerging evidence from studies that aim to address potential concerns. We also describe a translational framework that could be used to guide the development of a new generation of comprehensive research studies aimed at capitalizing on these exciting new discoveries.
全基因组关联研究已经确定了数千个遗传标记与复杂疾病风险(包括癌症)之间一致复制的关联。这些标记本身在风险预测中的作用有限;然而,当使用多个这些标记进行组合时,预测性能似乎与许多目前可用的临床预测因子相似。尽管如此,对于这些遗传标记在风险预测中的临床有效性和实用性,仍然存在不同的观点。因此,存在合理的担忧,为新的研究方向提供了依据。在此,我们概述了这一争论,并以前列腺癌为例,突出了旨在解决潜在问题的研究的新证据。我们还描述了一个转化框架,可用于指导旨在利用这些令人兴奋的新发现的新一代综合研究的发展。