Risk of Cancer in Cases of Suspected Lynch Syndrome Without Germline Mutation
Risk of Cancer in Cases of Suspected Lynch Syndrome Without Germline Mutation
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DOI：
10.1053/j.gastro.2013.01.044
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发表时间：
2013-05-01
期刊：
影响因子：
29.4
通讯作者：
Jover, Rodrigo
中科院分区：
文献类型：
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作者：
Rodriguez-Soler, Maria;Perez-Carbonell, Lucia;Jover, Rodrigo
背景与目的：伴有微卫星不稳定性（MSI）和不存在MLH1启动子超甲基化的错配修复（MMR）免疫组化缺陷的结直肠癌（crc）可能是由Lynch综合征引起的。一些患有这些癌症的患者没有发现致病性种系突变，被认为患有林奇样综合征（LLS）。这项研究的目的是确定LLS患者的家庭患癌症的风险。方法：我们研究了一个以人群为基础的队列，包括1705名连续的患者，进行MSI测试和MMR蛋白的免疫组织化学分析。当患者被发现有致病的种系突变时，就被诊断为Lynch综合征。MSI、MSH2和/或MSH6表达缺失、PMS2分离缺失或MLH1缺失但MLH1启动子超甲基化、无致病性突变的患者被认为患有LLS。比较两组患者的临床特征及家庭肿瘤经年龄和性别调整的标准化发病率（SIRs）。结果：LLS患者的家庭CRC发病率明显低于Lynch综合征确诊患者的家庭（Lynch综合征的SIR为6.04；95%可信区间[CI]为3.58 ~ 9.54；LLS的SIR为2.12；95% CI为1.16 ~ 3.56;P < .001）。然而，LLS患者家庭的CRC发病率高于散发性CRC家庭（散发性CRC SIR， 0.48; 95% CI, 0.27-0.79; P < 0.001）。结论：LLS家庭患癌风险低于Lynch综合征家庭，但高于散发性结直肠癌家庭。这些结果证实需要对这些患者及其亲属进行特殊的筛查和监测策略。
BACKGROUND & AIMS: Colorectal cancers (CRCs) with microsatellite instability (MSI) and a mismatch repair (MMR) immunohistochemical deficit without hypermethylation of the MLH1 promoter are likely to be caused by Lynch syndrome. Some patients with these cancers have not been found to have pathogenic germline mutations and are considered to have Lynch-like syndrome (LLS). The aim of this study was to determine the risk of cancer in families of patients with LLS. METHODS: We studied a population-based cohort of 1705 consecutive patients, performing MSI tests and immunohistochemical analyses of MMR proteins. Patients were diagnosed with Lynch syndrome when they were found to have pathogenic germline mutations. Patients with MSI and loss of MSH2 and/or MSH6 expression, isolated loss of PMS2 or loss of MLH1 without MLH1 promoter hypermethylation, and no pathogenic mutation were considered to have LLS. The clinical characteristics of patients and the age- and sex-adjusted standardized incidence ratios (SIRs) of cancer in families were compared between groups. RESULTS: The incidence of CRC was significantly lower in families of patients with LLS than in families with confirmed cases of Lynch syndrome (SIR for Lynch syndrome, 6.04; 95% confidence interval [CI], 3.58-9.54; SIR for LLS, 2.12; 95% CI, 1.16-3.56; P < .001). However, the incidence of CRC was higher in families of patients with LLS than in families with sporadic CRC (SIR for sporadic CRC, 0.48; 95% CI, 0.27-0.79; P < .001). CONCLUSIONS: The risk of cancer in families with LLS is lower that of families with Lynch syndrome but higher than that of families with sporadic CRC. These results confirm the need for special screening and surveillance strategies for these patients and their relatives.