Grisanzio Chiara, Freedman Matthew L
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Genes Cancer. 2010 Jun;1(6):555-9. doi: 10.1177/1947601910381380.
Genome-wide association studies (GWAS) have successfully identified common polymorphisms that are strongly associated with many traits, including cancer. A gene desert located on chromosome 8q24 is associated with multiple cancer types. One of the closest genes is the MYC proto-oncogene. Investigations are now turning toward a mechanistic understanding of these (and other) risk loci. Recent studies demonstrate that the 8q24 loci are enhancers and that they physically interact with MYC. A still unresolved issue is the absence of a consistent association between genotype status at the risk loci and steady-state MYC expression levels in adult human tissues. Clarifying the function of the 8q24 variants and their link to MYC regulation by further in vivo and in vitro functional studies will allow a deeper understanding of the mechanisms underlying human cancer development.
全基因组关联研究(GWAS)已成功鉴定出与包括癌症在内的许多性状密切相关的常见多态性。位于8号染色体q24区域的基因荒漠与多种癌症类型相关。最接近的基因之一是MYC原癌基因。目前研究正转向对这些(以及其他)风险位点的机制性理解。最近的研究表明,8q24位点是增强子,并且它们与MYC发生物理相互作用。一个尚未解决的问题是,在成年人体组织中,风险位点的基因型状态与MYC稳态表达水平之间缺乏一致的关联。通过进一步的体内和体外功能研究阐明8q24变体的功能及其与MYC调控的联系,将有助于更深入地理解人类癌症发生的潜在机制。