Germline mutations in mismatch repair genes: prevalence, risk of cancer, and environmental modifiers of risk.

目的:1。开发一个模型来预测谁在一组导致癌症的基因中有突变。估计这些基因（携带者）发生突变的人患癌症的风险。确定携带者患癌症的风险是否可以降低在一组被称为“错配修复基因”的基因中遗传突变的人患癌症的风险会增加，尤其是结肠癌和直肠癌。如果这些携带者能够被识别出来，他们就可以采取预防措施，如筛查，以降低他们患癌症和死亡的风险。我们将使用结肠癌家庭登记处（CFR）的数据开发一个模型，CFR是世界上最大的携带者和非携带者数据集，已经招募了来自澳大利亚、美国和加拿大的4000多个家庭并对其进行了基因测试。该模型将允许临床医生预测谁可能是基于携带者的，这样他们就可以进行突变检测。我们知道携带者患癌症的风险很高，但我们没有精确的估计。我们将使用冒号CFR应用复杂的统计方法来回答这个问题。这些数据对遗传咨询至关重要，因此患者和医生可以做出适当的决定，采取哪些预防措施。我们还将使用结肠CFR数据来找出癌症携带者与没有癌症的人有什么不同通过他们完成的生活方式问卷调查包括饮食，吸烟，饮酒，运动，阿司匹林的使用，口服避孕药的使用。我们可以确定携带者可以避免的风险因素（或者如果他们降低了癌症风险）来降低他们的癌症风险。

Aims: 1. Develop a model that will predict who has a mutation in a group of genes that cause cancer 2. Estimate risk of cancer in people who have a mutation in these genes (carriers) 3. Determine if cancer risk in carriers can be reduced People who inherit a mutation in a group of genes called 'mismatch repair genes' are at increased risk of cancer, particularly cancer of the colon and rectum. If these carriers can be identified they can take preventive measures such as screening to reduce their risk of cancer and death. We will develop a model using data from the Colon Cancer Family Registry (CFR), the world's largest dataset of carriers and non-carriers which has already recruited and genetically tested over 4,000 families from Australasia, USA and Canada. The model will allow clinicians to predict who is a likely be a carrier based so they can be tested for the mutation. We know the risk of cancer is high in carriers, but we don't have precise estimates. We will use the Colon CFR applying sophisticated statistical methods required to answer this question. This data is critical for genetic counselling so appropriate decisions can be made by the patient and the doctor as to what preventive measures to take. We will also use the Colon CFR data to find out what how the carriers who develop cancer differ from those who stay cancer free using their completed lifestyle questionnaires which includes questions on diet, smoking, alcohol consumption, exercise, aspirin use, and oral contraceptive pill use. We may identify risk factors that carriers can avoid (or take up if they reduce cancer risk) to reduce their risk of cancer.