Lowy Cancer Research Centre, Prince of Wales Hospital, Randwick NSW 2031, Australia.
J Clin Oncol. 2013 Jul 10;31(20):2554-62. doi: 10.1200/JCO.2012.46.8454. Epub 2013 Jun 3.
Molecular screening techniques are available to identify hereditary Lynch syndrome in people with newly diagnosed colorectal cancer (CRC). We aimed to determine whether decisions of patients or clinicians reduced detection of Lynch syndrome.
A prospective cohort of 245 consecutive individuals with mismatch repair-deficient CRC recruited from a population-based molecular screening program of all incident patient cases of CRC in a health care region of 1.2 million inhabitants. All incident CRCs were analyzed for mismatch repair protein loss, supported by BRAF mutation and microsatellite instability testing. Advice regarding referral for germline testing was provided to treating surgeons.
The mean age of patients was 72.5 ± standard deviation of 12 years; 64% were women; 65% had BRAF-mutant cancers. Consent for germline testing was received from 194 patients (79%): 120 with low and 74 with high likelihood of Lynch syndrome based on tumor molecular profile. Of patients who consented, 143 provided samples for germline analysis, with 12 of 143 showing a mutation (8.4%; 95% CI, 4.4% to 14.2%). Among the 102 patients who chose not to provide a sample or did not consent, an estimated 5.3 of 102 had germline mutations (5.2%; 95% CI, 2.0% to 17.5%).
A universal screening strategy for Lynch syndrome is potentially effective because the overall estimate of germline mutations was 17.3 of 245 patient cases (7.1%; 95% CI, 2.8% to 18.2%). However, the true value of screening is likely to be greatly limited by the decisions and circumstances of patients in taking up germline testing.
分子筛选技术可用于识别新诊断为结直肠癌（CRC）的遗传性林奇综合征患者。我们旨在确定患者或临床医生的决策是否降低了林奇综合征的检出率。
一项前瞻性队列研究纳入了 245 名连续确诊为错配修复缺陷型 CRC 的患者，这些患者均来自一个拥有 120 万居民的医疗区域的基于人群的分子筛选项目。对所有 CRC 病例均进行了错配修复蛋白缺失分析，并结合 BRAF 突变和微卫星不稳定性检测。为治疗外科医生提供了关于进行种系检测的建议。
患者的平均年龄为 72.5 ± 12 岁；64%为女性；65%的患者存在 BRAF 突变型肿瘤。194 名患者（79%）同意进行种系检测：120 名患者基于肿瘤分子特征低概率患有林奇综合征，74 名患者高概率患有林奇综合征。在同意进行种系检测的患者中，有 143 名患者提供了种系分析样本，其中 12 名（8.4%；95% CI，4.4%至 14.2%）发现了突变。在 102 名未提供样本或不同意提供样本的患者中，估计有 5.3 名（5.2%；95% CI，2.0%至 17.5%）患者存在种系突变。
林奇综合征的通用筛查策略具有潜在的有效性，因为总体估计种系突变的发生率为 245 例患者中有 17.3 例（7.1%；95% CI，2.8%至 18.2%）。然而，筛查的实际价值可能会因患者决定和接受种系检测的情况而受到极大限制。
