Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Nat Commun. 2019 May 14;10(1):2154. doi: 10.1038/s41467-019-09775-w.
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
结直肠癌（CRC）是全球癌症相关死亡的主要原因，并且具有很强的遗传基础。我们报告了一项针对 34627 例 CRC 病例和 71379 例欧洲血统对照的全基因组关联分析，该分析确定了 31 个新的 CRC 风险位点的 SNP。我们还在新的和以前报道的欧洲 CRC 位点以及以前仅在亚洲人群中发现的另外九个 CRC SNP 中确定了八个独立的风险 SNP。我们使用原位启动子捕获 Hi-C（CHi-C）、基因表达和计算机注释方法来识别 CRC SNP 的可能靶基因。虽然这些新的 SNP 关联暗示了富含已知 CRC 途径（如 Wnt 和 BMP）的靶基因，但它们也突出了与结直肠肿瘤发生没有先前联系的新途径。这些发现进一步深入了解了 CRC 的易感性，并提高了将遗传风险评分应用于个性化筛查和预防的前景。
