Centre for Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, United Kingdom.
Curr Opin Genet Dev. 2010 Jun;20(3):201-9. doi: 10.1016/j.gde.2010.03.012. Epub 2010 Apr 24.
Genome-wide association studies (GWAS) have led to the identification of more than 100 common, low-penetrance loci for cancer. At these loci, common genetic variants are associated with moderate increases in risk, typically <1.5-fold. Almost all loci lie in genomic regions not previously suspected to be involved in cancer. A plausible functional basis for a few loci, such as FGFR2 for breast cancer and MSMB for prostate cancer, has been elucidated, but the majority are not understood and suggest new mechanisms of carcinogenesis. Most loci are specific to a single cancer type, and are often subtype specific (e.g. ER-positive breast cancer). There are notable differences in the genetic architecture for different cancer types, with a greater contribution of common variants for prostate cancer. The clinical utility of variants to predict individual disease risk of disease is currently limited, but this may change as more variants are identified.
全基因组关联研究(GWAS)已鉴定出 100 多个常见的、低外显率的癌症易感基因座。在这些基因座中,常见的遗传变异与适度增加的风险相关,通常<1.5 倍。几乎所有的基因座都位于以前不被认为与癌症有关的基因组区域。少数基因座(如乳腺癌的 FGFR2 和前列腺癌的 MSMB)的合理功能基础已经阐明,但大多数基因座仍未得到理解,提示了新的致癌机制。大多数基因座是特定于单一癌症类型的,并且通常是亚型特异性的(例如 ER 阳性乳腺癌)。不同癌症类型的遗传结构存在显著差异,前列腺癌中常见变异的贡献更大。目前,变异预测个体疾病风险的临床应用有限,但随着更多变异的发现,这种情况可能会改变。