Genetic approaches to combating colorectal cancer

肠癌是一种常见且经常致命的疾病，每年在英国有43,000人患病，导致约16,000人死亡。基因和环境都在这种癌症的发展中起作用。我们的研究重点是了解基因和环境对肠癌易感性的相互作用，以及这些因素如何在分子、细胞和整个人的水平上导致癌症。我们使用最先进的技术来了解遗传和环境对肠癌风险的影响的全貌，并发现与癌症风险有因果关系的新基因变化。这包括对人类研究对象的整个遗传密码（DNA）进行测序，并使用基因分型阵列标记人类基因组成的部分。我们研究这些遗传变异在人类和动物模型系统中的影响。我们的目标是找到预防癌症形成的新方法，并已开始在人体中进行临床研究，以探索维生素D对人体肠道内膜的有益作用。我们还能够使用一种称为“基因组编辑”的系统，改变从人类肠道（肠道类器官）中培养出来的细胞的遗传密码。这使我们能够直接测试与癌症风险相关的遗传信号的影响。我们还可以使用基因组编辑方法来逆转这些影响，并测试药物和饮食成分对类器官和动物模型系统的有益影响。在未来，我们计划在人体研究中测试这些药物的效果。凭借我们独特的发现科学，疾病模型和将实验室发现转化为临床的能力，我们非常有能力通过早期发现和癌症预防，在常见癌症杀手领域对人类健康产生有益的影响。

Cancer of the large bowel, is a common and frequently fatal disease, affecting 43,000 people in the UK annually and causing ~16,000 deaths. Genes and environment both play a role in development of this cancer. Our research focuses on understanding the interplay of genes and environment on bowel cancer susceptibility and how these cause cancer at a molecular, cellular and whole-person level. We use state-of-the-art technologies to understand the complete picture of genetic and environmental effects on bowel cancer risk and find new genetic changes causally linked with cancer risk. This includes sequencing the entire genetic code (DNA) of human research subjects, and using genotyping arrays to tag parts of the human genetic makeup. We study the effects of these genetic variants in model systems from humans and animals. We aim to identify new ways to prevent cancers forming, and have begun clinical studies in humans to explore the beneficial effects of vitamin D on the lining of the human bowel. We are also able to change the genetic code in cells that we grow from the human bowel (intestinal organoids) using a system called “genome-editing”. This allows us to directly test the effects of genetic signals associated with cancer risk. We can also use genome editing approaches to reverse these effects and test the beneficial effects of drugs, and dietary components, on organoid and animal model systems. In future, we plan to test the effects of these agents in human studies. With our unique blend of discovery science, disease models and ability to translate laboratories findings to the clinic, we are extremely well-placed to make beneficial impact in human health in the field of a common cancer killer through early detection and cancer prevention.