Dove-Edwin Isis, de Jong Andrea E, Adams Joanna, Mesher David, Lipton Lara, Sasieni Peter, Vasen Hans F A, Thomas Huw J W
Family Cancer Group, Cancer Research, UK Colorectal Cancer Unit, St. Mark's Hospital, Watford Road, Harrow, Middlesex, United Kingdom.
Gastroenterology. 2006 Jun;130(7):1995-2000. doi: 10.1053/j.gastro.2006.03.018.
BACKGROUND & AIMS: Lynch syndrome is an autosomal dominant predisposition to colorectal cancer caused by mutations in DNA mismatch repair genes; colorectal cancer risk is high. Few studies have addressed colorectal cancer risk in individuals from dominant families without mismatch repair deficiency. We sought to establish whether these individuals are also at increased risk by examining the incidence of advanced neoplasia during surveillance.
In this prospective cohort study, BAT26 testing of tumors was carried out at 2 tertiary centers on 125 individuals from 97 families (with a dominant colorectal cancer history) to classify families as Lynch syndrome (microsatellite unstable) or non-Lynch syndrome (microsatellite stable). Colonoscopy results in 288 at-risk family members were compared.
Twenty-nine families were classified as Lynch syndrome and 68 as non-Lynch syndrome. Seven hundred seventy-six colonoscopies were undertaken. High-risk adenomas occurred in 7 of 91 (7.7%) Lynch syndrome individuals and 15 of 197 (7.6%) non-Lynch syndrome individuals, adjusted relative risk 1.15 (95% CI: 0.6-2.3). Cancer was observed only in Lynch syndrome individuals (4/91; 4.4%), Fisher exact test, P = .010. Multiple adenomas were only seen in non-Lynch syndrome individuals (13/197; 6.6%), Fisher exact text, P = .06.
Individuals with an autosomal dominant family history of colorectal cancer with and without evidence of Lynch syndrome are at equal risk of high-risk adenomas during surveillance, but colorectal cancer was only seen in Lynch syndrome. Therefore non-Lynch syndrome individuals do require colonoscopic surveillance, but the interval could be lengthened because risk of (interval) cancer is low. Lynch syndrome individuals require short surveillance intervals as is the recommended practice.
林奇综合征是一种由DNA错配修复基因的突变引起的常染色体显性遗传性结直肠癌易感性疾病，患结直肠癌的风险很高。很少有研究探讨无错配修复缺陷的显性家族个体的结直肠癌风险。我们试图通过检查监测期间高级别瘤变的发生率来确定这些个体是否也有增加的风险。
在这项前瞻性队列研究中，在2个三级中心对来自97个家族（有显性结直肠癌病史）的125名个体的肿瘤进行BAT26检测，以将家族分类为林奇综合征（微卫星不稳定）或非林奇综合征（微卫星稳定）。比较288名高危家庭成员的结肠镜检查结果。
29个家族被分类为林奇综合征，68个家族被分类为非林奇综合征。共进行了776次结肠镜检查。91名林奇综合征个体中有7名（7.7%）发生高危腺瘤，197名非林奇综合征个体中有15名（7.6%）发生高危腺瘤，校正相对风险为1.15（95%可信区间：0.6 - 2.3）。仅在林奇综合征个体中观察到癌症（4/91；4.4%），Fisher精确检验，P = 0.010。仅在非林奇综合征个体中观察到多发腺瘤（13/197；6.6%），Fisher精确检验，P = 0.06。
有或无林奇综合征证据的常染色体显性遗传性结直肠癌家族史个体在监测期间发生高危腺瘤的风险相同，但仅在林奇综合征个体中观察到结直肠癌。因此，非林奇综合征个体确实需要进行结肠镜监测，但由于（间隔期）癌症风险较低，监测间隔可以延长。林奇综合征个体需要按照推荐的做法进行短间隔监测。
