Lynch syndrome-associated endometrial cancer: prevention, screening and prognosis

林奇综合征是由特定的基因缺陷引起的，这些缺陷使癌症更有可能发生。林奇综合征有家族遗传。肠癌和子宫癌在患有林奇综合征的人中更常见。当我们知道某人患有林奇综合征时，我们会提供结肠镜检查，这是一种摄像测试，可以检查肠道内部，在肠息肉癌变之前将其切除。这已经被证明可以拯救生命。为了预防子宫癌，一些女性在她们的家庭结束后会进行子宫切除术。其他人进行了子宫癌筛查或接受激素治疗，尽管我们不知道这些方法是否有效。多达十分之一的患有子宫癌的女性可能患有林奇综合征，尽管大多数人并不知道。如果他们知道林奇综合征，他们可能会选择定期进行结肠镜检查，以切除肠道息肉。他们还可能帮助其他家庭成员查明他们是否患有林奇综合症。在患有林奇综合征的妇女中发生的子宫癌与在没有林奇综合征的妇女中发生的子宫癌可能表现不同，并且具有不同的前景。在这个项目中，我将进行三项研究：在研究1中，我将观察有多少患有子宫癌的患者患有他们不知道的林奇综合征。我们可以通过对肿瘤进行特定的实验室测试来发现这一点。我将观察200名女性，她们在接受子宫切除术时为未来的研究项目捐献了血液和肿瘤样本。我还将对200名新诊断为子宫癌的妇女进行检查，因为她们正在接受外科手术。如果肿瘤研究表明林奇综合征可能存在，我们将进行血液测试，以确定是否存在基因缺陷。这将在储存的血液样本上进行，或者对于目前的患者，将通过我们医院的遗传咨询服务进行基因测试。我们将找出有多少患有子宫癌的女性患有林奇综合征。我还会发现，对患有子宫癌的女性进行林奇综合征测试是多么简单。我会看看病人是否乐于接受林奇综合征的肿瘤检测，以及他们是否准备接受遗传咨询。我会看看他们是否想接受结肠镜检查来识别和治疗肠息肉。我还将看看对患有子宫癌的女性进行林奇综合征筛查可能需要多少费用。这将有助于我们制定指导方针，指导将来哪些子宫癌患者应该接受林奇综合征测试。在研究2中，我将比较患有林奇综合征的女性和没有患子宫癌的女性的子宫癌。使用专门的实验室技术，我将看看这些肿瘤是如何不同的，它们是如何相同的。我会看看患有林奇综合征的女性比没有患有子宫癌的女性更有可能还是更少地死于子宫癌。这将有助于我们更多地了解子宫癌，并在未来更好地告知患者。研究3将考察子宫癌筛查和激素治疗在预防患有林奇综合征的女性子宫癌方面的有效性。我会看看超重和不运动是否会增加患有林奇综合症的女性患子宫癌的可能性。这将帮助我们在女性知道自己患有林奇综合征时给她们适当的建议。

Lynch syndrome is caused by specific gene faults that make cancer more likely to occur. Lynch syndrome runs in families. Bowel cancer and womb cancer are more common in people with Lynch syndrome. When we know someone has Lynch syndrome, we offer colonoscopy, a camera test to look inside the bowel, to remove any bowel polyps before they become cancerous. This has been shown to save lives. To prevent womb cancer, some women have a hysterectomy once their family is complete. Others have womb cancer screening or take hormone treatments, even though we do not know if these things work. As many as 1 in 10 women with womb cancer may have Lynch syndrome, although most do not know it. If they knew about the Lynch syndrome, they may choose to have regular screening by colonoscopy to remove bowel polyps. They may also help other family members find out whether they have Lynch syndrome. Womb cancer that develops in women with Lynch syndrome may behave differently and have a different outlook compared with womb cancer that occurs in women without Lynch syndrome. No one has looked at this before.In this project, I will be conducting three studies: In Study 1, I will see how many patients with womb cancer have Lynch syndrome that they didn't know about. We can find this out by carrying out specific laboratory tests on the tumours. I will look at 200 women who gave blood and tumour samples for future research projects when they came in for their hysterectomy. I will also test 200 women with new diagnoses of womb cancer as they come through the department for their surgery. If the tumour studies suggest that Lynch syndrome may be present, we will carry out blood tests to see if the gene fault is there. This will be done on the stored blood sample or, for current patients, genetic testing will be carried out through the genetic counselling service in our hospital. We will find out how many women with womb cancer have Lynch syndrome. I will also find out how straightforward it is to test women with womb cancer for Lynch syndrome. I will see whether patients are happy for their tumours to be tested for Lynch syndrome and whether they are prepared to go for genetic counselling. I will see whether they want to undergo colonoscopy to identify and treat bowel polyps. I will also see how much screening for Lynch syndrome in women with womb cancer is likely to cost. This will help us develop guidelines for which patients with womb cancer should be tested for Lynch syndrome in the future. In Study 2, I will compare womb cancers from women who have Lynch syndrome with those who do not. Using specialised laboratory techniques, I will look to see how the tumours are different and how they are the same. I will look at whether the women with Lynch syndrome were more or less likely to die from their womb cancer than women without. This will help us understand womb cancer more and inform patients better in the future. Study 3 will look at how effective womb cancer screening and hormone treatments are at preventing womb cancer in women with Lynch syndrome. I will see whether being overweight and inactive make womb cancer more likely in women with Lynch syndrome. This will help us advise women properly when they know they have Lynch syndrome.