CEF生殖中心分享何为林奇综合征？

Article: Genetics and cancer screening

文章：基因学和癌症基因筛查

Author: Megan Cheney

Book: Office Care of Women

书籍：女性门诊护理

Published by: Cambridge University Press

出版社：剑桥大学出版社

Editors: Botros RMB Rizk

Martin Olsen

主编： Botros RMB Rizk

Martin Olsen

Approximately 20%-30% of colorectal cancers are related to an inherited genetic mutation, the most common of which is an autosomal dominant condition called Lynch syndrome.

大约20%-30%的结直肠癌与遗传性基因突变有关，其中最常见的是林奇综合征，这是一种常染色体显性遗传病。

Lynch syndrome accounts for 3% of newly diagnosed cases of colorectal cancer, but it is also associated with extracolonic malignancies such as cancers of the endometrium, urinary tract, ovary, stomach, hepatobiliary tract, small bowel, brain, or skin (1).

结直肠癌中约有3%的病例是由于林奇综合征引起的。林奇综合征也跟结肠外恶性肿瘤有关，例如子宫内膜癌、泌尿道癌、卵巢癌、胃癌、肝胆道癌、小肠癌、脑癌或皮肤癌（1）。

About 2% of endometrial cancers are associated with Lynch syndrome and have an average age at the time of diagnosis of 50. As many as 20% of Lynch syndrome inpiduals will have an extracolonic cancer. Women with Lynch syndrome have a 21%-60% risk of endometrial cancer and a 0.3%-20% risk of ovarian cancer (2).

大约2%的子宫内膜癌是由林奇综合征引起的，患者确诊时的平均年龄为50岁。多达20%的林奇综合征患者患有结肠外癌。林奇综合症女性患者患子宫内膜癌的风险为21%-60%，患卵巢癌的风险为0.3%-20%（2）。

Lynch syndrome is sometimes referred to as hereditary nonpolyposis colorectal cancer (HNPCC) to differentiate it from other inherited colorectal cancers such as familiar adenomatous polyposis. But since some cases of Lynch syndrome have been found to have adenomatous polyps, it is more accurately referred to as Lynch syndrome to specifically refer to inpiduals with a germline mutation in a DNA mismatch repair gene (such as MSH2, MLH1, MSH6, or PMS2) or loss of expression of the MSH2 gene due to deletion in the EPCAM gene.

林奇综合征也被称为遗传性非息肉病性结直肠癌（HNPCC），以区别于其他遗传性结直肠癌，例如常见的腺瘤性息肉病。但由于在一些林奇综合征患者体内也发现了腺瘤性息肉，因此其更准确的命名是林奇综合征，特指DNA 错配修复基因（如 MSH2、MLH1、MSH6 或 PMS2）或由于 EPCAM 基因缺失导致 MSH2 基因表达缺失而导致的种系突变。

The majority of Lynch syndrome, approximately 90%, is caused by a germline mutation in either MSH2 or MLH1 which carry a 30%-74% lifetime risk of colorectal cancer (2). However, other less frequent mutations such as a mutation in MSH6 carry a lower lifetime risk of colorectal cancer of 10%-22% and a later onset but a higher lifetime risk of endometrial cancer of 71% (2).

大多数林奇综合征（约90%）是由 MSH2 或 MLH1突变导致，患者一生患结直肠癌的风险为30%-74%（2）。其他不太常见的突变导致的结直肠癌风险较低，例如MSH6突变为 10%-22%，虽然其发病较晚，但一生患子宫内膜癌的风险较高，为71%（2）。

Increased surveillance is recommended for inpiduals affected with Lynch syndrome or at high risk for Lynch syndrome. In a prospective observational study by Dove-Edwin et al., colonoscopy screening among Lynch syndrome families resulted in a 72% decrease in mortality (3). The US Multi-Society Task Force concluded that colonoscopy screening in persons affected with Lynch syndrome or first-degree relatives of those affected should occur every one or two years before the youngest age of diagnosis in the family if diagnosed before the age of 25. They also concluded that women affected by or at risk of Lynch syndrome should be offered endometrial cancer screening with annual pelvic exams and endometrial sampling and ovarian cancer screening with annual transvaginal ultrasound beginning at age 30-35 years.

建议对林奇综合征患者或林奇综合征高风险人群增加检查。Dove-Edwin等人的一项前瞻性观察研究发现，对有林奇综合征家庭病史的人群进行结肠镜检查后，死亡率降低了72%（3）。美国多学会工作组总结：如果家族中有人在25岁前确诊，那么最好在家族中最小的诊断年龄之前每一两年对患有林奇综合征的人或其直系亲属进行结肠镜检查。他们还建议为林奇综合征患者或有风险的妇女提供子宫内膜癌筛查，每年进行一次盆腔检查和子宫内膜取样，以及从30-35岁开始每年通过经阴道超声进行卵巢癌筛查。

References

参考文献

1．Salovaara R, Loukkola A, Kristo P, et al. Population-based molecular detection of hereditary nonpolyposis colorectal cancer. J Clin Oncol 2000; 182:193-200.

2. Giardiello FM, Allen JI, Axibund JE, et al. AGA Section Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on colorectal cancer. Gastroenterology 2014; 147:507-26.

3. Dove-Edwin I, Sasieni P, Adams J, et al. Prevention of colorectal cancer by colonoscopy surveillance in inpiduals with a family history of colorectal cancer: 16 year, prospective, follow-up study. BMJ 2005; 331:1047.