To inform effective genomic medicine strategies, it is important to examine current approaches and gaps in well-established applications. Lynch syndrome (LS) causes 3–5% of colorectal cancers (CRCs). While guidelines commonly recommend LS tumour testing of all CRC patients, implementation in health systems is known to be highly variable. To provide insights on the heterogeneity in practice and current bottlenecks in a high-income country with universal healthcare, we characterise the approaches and gaps in LS testing and referral in seven Australian hospitals across three states. We obtained surgery, pathology, and genetics services data for 1,624 patients who underwent CRC resections from 01/01/2017 to 31/12/2018 in the included hospitals. Tumour testing approaches differed between hospitals, with 0–19% of patients missing mismatch repair deficiency test results (total 211/1,624 patients). Tumour tests to exclude somatic MLH1 loss were incomplete at five hospitals (42/187 patients). Of 74 patients with tumour tests completed appropriately and indicating high risk of LS, 36 (49%) were missing a record of referral to genetics services for diagnostic testing, with higher missingness for older patients (0% of patients aged ≤ 40 years, 76% of patients aged > 70 years). Of 38 patients with high-risk tumour test results and genetics services referral, diagnostic testing was carried out for 25 (89%) and identified a LS pathogenic/likely pathogenic variant for 11 patients (44% of 25; 0.7% of 1,624 patients). Given the LS testing and referral gaps, further work is needed to identify strategies for successful integration of LS testing into clinical care, and provide a model for hereditary cancers and broader genomic medicine. Standardised reporting may help clinicians interpret tumour test results and initiate further actions.

中文翻译：

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在全民医疗保健的高收入国家对结直肠癌患者进行林奇综合征检测：​​对澳大利亚七家医院当前实践和差距的回顾性研究

为了提供有效的基因组医学策略，重要的是检查当前的方法和成熟应用中的差距。林奇综合征 (LS) 导致 3-5% 的结直肠癌 (CRC)。虽然指南通常建议对所有 CRC 患者进行 LS 肿瘤检测，但众所周知，卫生系统的实施情况存在很大差异。为了深入了解具有全民医疗保健的高收入国家实践中的异质性和当前的瓶颈，我们描述了澳大利亚三个州的七家医院在 LS 检测和转诊方面的方法和差距。我们获得了 2017 年 1 月 1 日至 2018 年 12 月 31 日期间在所纳入医院接受 CRC 切除术的 1,624 名患者的手术、病理和遗传学服务数据。不同医院的肿瘤检测方法不同，0-19% 的患者缺少错配修复缺陷检测结果（总共 211/1,624 名患者）。五家医院（42/187 名患者）的排除体细胞 MLH1 丢失的肿瘤检测不完整。在 74 名正确完成肿瘤检测并显示 LS 高风险的患者中，36 名 (49%) 缺少转诊至遗传学服务机构进行诊断检测的记录，老年患者的缺失率更高（年龄 ≤ 40 岁的患者为 0%，76年龄 > 70 岁的患者百分比）。在 38 名具有高风险肿瘤检测结果并转诊至遗传学服务的患者中，对 25 名患者（89%）进行了诊断检测，并确定了 11 名患者的 LS 致病性/可能致病性变异（25 名患者中的 44%；1,624 名患者中的 0.7%） 。鉴于 LS 测试和转诊差距，需要进一步开展工作来确定将 LS 测试成功整合到临床护理中的策略，并为遗传性癌症和更广泛的基因组医学提供模型。标准化报告可以帮助临床医生解释肿瘤检测结果并采取进一步行动。