Slager Susan L, Kay Neil E, Fredericksen Zachary S, Wang Alice H, Liebow Mark, Cunningham Julie M, Vachon Celine M, Call Timothy G, Cerhan James R
Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
Br J Haematol. 2007 Dec;139(5):762-71. doi: 10.1111/j.1365-2141.2007.06872.x.
Common genetic variants are thought to increase the risk of chronic lymphocytic leukaemia (CLL), and case-control studies provide an approach to detect these variants. There have been multiple candidate gene studies published to date, but relatively few disease pathway studies or large genomic association studies. We summarize the results of these previous studies, as well as present results from our recent large pathway study of 9412 single nucleotide polymorphisms from 1253 immunity and inflammation genes in a study of 126 CLL cases and 484 frequency-matched controls. Several promising genes have been identified as susceptibility genes for risk of CLL across all of these association studies. However, a number of candidate gene studies have not been replicated in follow-up studies, whereas the results from disease pathway and large genomic studies have yet to be replicated in an independent sample. The challenge of future studies of this type will be overcoming study design issues, including definition of CLL, sample size limitations and multiple testing issues.
常见基因变异被认为会增加慢性淋巴细胞白血病（CLL）的风险，病例对照研究提供了一种检测这些变异的方法。迄今为止，已经发表了多项候选基因研究，但疾病通路研究或大型基因组关联研究相对较少。我们总结了这些先前研究的结果，以及我们最近对126例CLL病例和484例频率匹配对照进行的大型通路研究的结果，该研究涉及1253个免疫和炎症基因中的9412个单核苷酸多态性。在所有这些关联研究中，已经确定了几个有前景的基因作为CLL风险的易感基因。然而，一些候选基因研究在后续研究中未得到重复验证，而疾病通路和大型基因组研究的结果尚未在独立样本中得到重复验证。此类未来研究的挑战将是克服研究设计问题，包括CLL的定义、样本量限制和多重检验问题。
