Hard Work Ahead: Fine Mapping and Functional Follow-up of Susceptibility Alleles in Cancer GWAS

摘要: Genome-wide association studies (GWAS) in cancer have successfully identified over 450 regions that harbor susceptibility alleles with small effects contributing to the risk of one or more cancers. Less than 10 % thus far are common cancer, but it is these which display pleiotropy especially informative and provide new opportunities gain insights into mechanisms carcinogenesis. Since GWAS age has been notable for scalability, large-scale consortia combined many identify novel associated cancer. In fact, cancers, a substantial fraction markers identified, additional cumulative “polygenic” effect large scans further suggest remain be characterized. The emerging catalog variants, represents underlying genetic architecture susceptibility, already constitutes set cancers could used stratification public health measures. On other hand, discovery occurring at rate exceeds our capacity understand biology each allele. Nearly all variants point towards changes regulation key genes pathways not protein coding resulting “drivers” somatic alterations. Further investigation region depends upon sequence fine mapping (e.g., identification correlated variants) using silico functional tools nominate most promising detailed laboratory follow-up studies. Each interrogated individually, taking account unique features genomic locale order biological underpinnings variants. Building comprehensive alleles, across spectrum frequencies sizes, annotation should instrumental revealing eventually precision prevention.