Lindor Noralane M, Petersen Gloria M, Hadley Donald W, Kinney Anita Y, Miesfeldt Susan, Lu Karen H, Lynch Patrick, Burke Wylie, Press Nancy
Department of Medical Genetics, Mayo Clinic College of Medicine, Rochester, Minn, USA.
JAMA. 2006 Sep 27;296(12):1507-17. doi: 10.1001/jama.296.12.1507.
About 2% of all colorectal cancer occurs in the context of the autosomal dominantly inherited Lynch syndrome, which is due to mutations in mismatch repair genes. Potential risk-reducing interventions are recommended for individuals known to have these mutations.
To review cancer risks and data on screening efficacy in the context of Lynch syndrome (hereditary nonpolyposis colorectal cancer) and to provide recommendations for clinical management for affected families, based on available evidence and expert opinion.
A systematic literature search using PubMed and the Cochrane Database of Systematic Reviews, reference list review of retrieved articles, manual searches of relevant articles, and direct communication with other researchers in the field. Search terms included hereditary non-polyposis colon cancer, Lynch syndrome, microsatellite instability, mismatch repair genes, and terms related to the biology of Lynch syndrome. Only peer-reviewed, full-text, English-language articles concerning human subjects published between January 1, 1996, and February 2006 were included. The US Preventive Services Task Force's 2-tier system was adapted to describe the quality of evidence and to assign strength to the recommendations for each guideline.
The evidence supports colonoscopic surveillance for individuals with Lynch syndrome, although the optimal age at initiation and frequency of examinations is unresolved. Colonoscopy is recommended every 1 to 2 years starting at ages 20 to 25 years (age 30 years for those with MSH6 mutations), or 10 years younger than the youngest age of the person diagnosed in the family. While fully acknowledging absence of demonstrated efficacy, the following are also recommended annually: endometrial sampling and transvaginal ultrasound of the uterus and ovaries (ages 30-35 years); urinalysis with cytology (ages 25-35 years); history, examination, review of systems, education and genetic counseling regarding Lynch syndrome (age 21 years). Regular colonoscopy was favored for at-risk persons without colorectal neoplasia. For individuals who will undergo surgical resection of a colon cancer, subtotal colectomy is favored. Evidence supports the efficacy of prophylactic hysterectomy and oophorectomy.
The past 10 years have seen major advances in the understanding of Lynch syndrome. Current recommendations regarding cancer screening and prevention require careful consultation between clinicians, clinical cancer genetic services, and well-informed patients.
所有结直肠癌中约2%发生于常染色体显性遗传的林奇综合征，这是由错配修复基因的突变所致。对于已知有这些突变的个体，建议采取潜在的降低风险干预措施。
回顾林奇综合征（遗传性非息肉病性结直肠癌）背景下的癌症风险及筛查效果数据，并根据现有证据和专家意见为受影响家庭提供临床管理建议。
使用PubMed和Cochrane系统评价数据库进行系统文献检索，对检索文章的参考文献列表进行回顾，手工检索相关文章，并与该领域的其他研究人员直接沟通。检索词包括遗传性非息肉病性结肠癌、林奇综合征、微卫星不稳定性、错配修复基因以及与林奇综合征生物学相关的术语。仅纳入1996年1月1日至2006年2月期间发表的、经同行评审的、关于人类受试者的全文英文文章。采用美国预防服务工作组的两级系统来描述证据质量，并为每条指南的建议赋予强度。
证据支持对林奇综合征患者进行结肠镜监测，尽管开始监测的最佳年龄和检查频率尚未确定。建议从20至25岁开始（有MSH6突变者为30岁），或比家族中确诊的最年轻患者年龄小10岁开始，每1至2年进行一次结肠镜检查。在充分认识到缺乏已证实疗效的情况下，还建议每年进行以下检查：子宫内膜取样以及子宫和卵巢的经阴道超声检查（30 - 35岁）；尿液分析及细胞学检查（25 - 35岁）；关于林奇综合征的病史、检查、系统回顾、教育和遗传咨询（21岁）。对于无结直肠肿瘤的高危人群，倾向于定期进行结肠镜检查。对于将接受结肠癌手术切除的个体，倾向于进行次全结肠切除术。证据支持预防性子宫切除术和卵巢切除术的疗效。
在过去10年中，对林奇综合征的认识取得了重大进展。目前关于癌症筛查和预防的建议需要临床医生、临床癌症遗传服务机构和充分知情的患者之间进行仔细的协商。
