Center for Clinical Epidemiology, St. Luke's Life Science Institute, 10-1 Akashi-cho, Chuo-ku, Tokyo, Japan.
Int J Hematol. 2013 Jan;97(1):3-19. doi: 10.1007/s12185-012-1220-9. Epub 2012 Dec 13.
Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and efforts to understand its etiology has followed a paradigm that common genetic variation in the presence of modifiable environmental factors contribute to disease risk. To date, there are numerous reports of candidate gene association studies suggesting an involvement of genetic loci in childhood ALL risk, but the general lack of consistency in results has underscored the need for careful interpretation and confirmation in additional well-designed studies. Complementary efforts using the genome-wide association study approach have shown indisputable evidence that common low penetrance genetic polymorphisms contribute to childhood ALL risk. However, current calculations show that these established disease loci only explain a portion of the total estimated contribution of common genetic variation on childhood ALL risk. Certain candidate gene loci previously examined likely contribute to this unexplained variation in risk, but the challenge moving forward will be to establish which ones based on the accumulating evidence. In this review, we describe the results of the most recent gene association studies in childhood ALL and discuss options for future efforts to advance this area of research.
急性淋巴细胞白血病（ALL）是儿童中最常见的癌症，人们致力于了解其病因，遵循这样一种模式，即常见的遗传变异与可改变的环境因素共同导致疾病风险。迄今为止，有大量关于候选基因关联研究的报告表明，遗传位点参与了儿童 ALL 风险，但结果普遍缺乏一致性，这突显了在更多精心设计的研究中进行仔细解释和确认的必要性。使用全基因组关联研究方法的补充研究无可置疑地表明，常见的低外显率遗传多态性会增加儿童 ALL 的风险。然而，目前的计算表明，这些已确定的疾病位点仅解释了常见遗传变异对儿童 ALL 风险的总估计贡献的一部分。先前检查过的某些候选基因位点可能导致风险的这种无法解释的变异，但未来的挑战将是根据不断积累的证据确定是哪些基因位点。在这篇综述中，我们描述了儿童 ALL 中最新的基因关联研究的结果，并讨论了推进这一研究领域的未来工作的选择。
