HNPCC-Register, Department of Gastroenterology, Hvidovre University Hospital, Copenhagen University, Denmark.
Cancer Epidemiol. 2009 Oct;33(3-4):231-4. doi: 10.1016/j.canep.2009.06.007. Epub 2009 Sep 12.
Optimal prevention of hereditary cancer is central and requires initiation of surveillance programmes and/or prophylactic measures at a safe age. Anticipation, expressed as an earlier age at onset in successive generations, has been demonstrated in hereditary nonpolyposis colorectal cancer (HNPCC). We specifically addressed anticipation in phenotypic HNPCC families without disease-predisposing mismatch repair (MMR) defects since risk estimates and age at onset are particularly difficult to determine in this cohort. The national Danish HNPCC register was used to identify families who fulfilled the Amsterdam criteria for HNPCC and showed normal MMR function and/or lack of disease-predisposing MMR gene mutation. In total, 319 cancers from 212 parent-child pairs in 99 families were identified. A paired t-test and a bivariate statistical model were used to assess anticipation. Both methods demonstrated an effect from anticipation with cancer diagnosed mean 11.4 years (t-test, p<0.0001) and mean 5.9 (bivariate model, p=0.02) years earlier in children than in parents. This observation suggests that anticipation may apply also to families without identified mutations and serves as a reminder to initiate surveillance programmes at young age also in HNPCC families with undefined genetic causes.
遗传性癌症的最佳预防是核心，需要在安全的年龄开始进行监测计划和/或预防措施。在遗传性非息肉病性结直肠癌（HNPCC）中已经证明了预期，即连续几代的发病年龄更早。我们专门针对表型 HNPCC 家族中没有疾病易感性错配修复（MMR）缺陷的预期进行了研究，因为在这一组中，风险估计和发病年龄特别难以确定。使用丹麦全国性的 HNPCC 登记处来确定符合阿姆斯特丹 HNPCC 标准且显示正常 MMR 功能和/或缺乏疾病易感性 MMR 基因突变的家族。在 99 个家族的 212 对父母-子女中，共确定了 319 例癌症。使用配对 t 检验和双变量统计模型来评估预期。两种方法均表明存在预期效应，即儿童的癌症诊断平均比父母早 11.4 年（t 检验，p<0.0001）和平均早 5.9 年（双变量模型，p=0.02）。这一观察结果表明，即使在没有确定突变的家族中，也可能存在预期，这提醒我们即使在遗传原因不明的 HNPCC 家族中，也应在年轻时开始进行监测计划。
