Germline epimutations of tumour suppressor genes in familial cancer

在肠癌的情况下，对我们社区疾病模式的研究表明，高达20%的肠癌具有遗传成分。我们现在知道这些病例中有高达4%的遗传异常。我们最近发现了一种以前未被认识到的癌症原因。受这种疾病影响的人可能在肠道以及乳腺和子宫中患有癌症。在这种情况下，基因字母表是正确的，但基因被化学修饰。这种变化被称为甲基化，意味着某些基因被拼写错误或根本没有。到目前为止，我们已经发现两个人有这个问题。我们的工作表明，这些个体遗传了一种遗传变化，并有可能将这种变化传递给他们的后代。这份拨款申请旨在正式追求这一发现。我们将研究一组癌症的遗传原因仍然未知的人。这些人的血液样本将被检查其DNA的甲基化。一个成功的项目将导致对这种新型遗传性癌症的全面描述，从而作为识别和有效管理有这种疾病风险的人和家庭的基础。很可能，识别出有癌症“风险”的个体将使我们能够实施预防性筛查策略。我们也将能够为那些没有遗传甲基化异常的家庭成员提供保证。

In the case of bowel cancer, studies of the pattern of disease in our community indicate that up to 20% of all bowel cancers has a inherited component . We now know the genetic abnormality in up to 4% of these cases. We have recently discovered a previously unrecognised cause of cancer. Individuals who are affected by this disease may have cancer in the bowel, as well as the breast and womb. In this condition the gene alphabet is correct but the genes are chemically modified. This change called methylation means that certain genes are spelt incorrectly or not at all. To date we have found two individuals who have this problem. Our work has shown that these individuals have inherited a genetic change and potentially could pass this change on to their offspring. This grant application seeks to formally pursue this findng. We will study a group of people in whom the genetic cause for their cancer remains unknown. Blood samples from these individuals will be examined for methylation of their DNA. A successful project will lead to a full description of this new type of hereditary cancer, and thus serve as the basis for identifying and effectively managing people and families at risk of this disease. It is likely that identification of individuals who are 'at risk' of cancer will allow us to implement preventative screening strategies. We will also be able to provide reassurance to those family members who have not inherited the methylation abnormality.