一项多中心国际研究中CDH1携带者的结肠镜检查结果。
Colonoscopy findings in CDH1 carriers from a multicenter international study.
作者信息
Chatterjee Arjun, Hüneburg Robert, Yang Qijun, Morrison Shannon, Bettzüge Anna, Marwitz Tim, Aretz Stefan, Spier Isabel, Ripperger Tim, Redler Silke, Kachanov Mykyta, Volk Alexander E, Vangala Deepak B, Daum Severin, Holinski-Feder Elke, Steinke-Lange Verena, Bahlke Kathrin, Strassburg Christian P, MejiaPerez Lady Katherine, O'Malley Margaret M, LaGuardia Lisa, Liska David, Macaron Carole, Sommovilla Joshua, Burke Carol A, Nattermann Jacob
机构信息
Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA.
Department of Internal Medicine, University Hospital Bonn, Bonn, Germany.
出版信息
Fam Cancer. 2025 May 5;24(2):44. doi: 10.1007/s10689-025-00466-8.
Germline (likely-)pathogenic variants (PV) in CDH1 predispose carriers to hereditary diffuse gastric cancer and lobular breast cancer. Previous studies from the United States suggest CDH1 variant carriers have an increased risk for adenomas or sessile serrated lesions (SSL), yet data linking CDH1 PVs and colorectal neoplasia are scarce. We aimed to investigate colonoscopy findings in CDH1 PVs. Adults carrying a PV/LPV in CDH1 with ≥ 1 colonoscopy between 01/01/2004-12/31/2023 were included. Patients were sourced from the David G. Jagelman Inherited Colorectal Cancer Registries at Cleveland Clinic and the German Consortium for Familial Intestinal Cancer. 103 CDH1 PV carriers were included. Most were female (66%) and white (93.1%). The median age at first colonoscopy was 47 years. The adenoma detection rate (ADR) was 29.4% (95% CI:19.9-41.1%) in the German cohort and 48.6% (95% CI: 33.0-64.4%) in the Cleveland cohort (p = 0.055) and significantly correlated with age (< 45 years, 13.6% (95% CI: 6.40-26.7%); 45-49 years, 52.4% (95% CI: 32.4-71.7%); ≥50 years, 52.6% (95% CI: 37.3-67.5%); p < 0.001). The ADR in Cleveland was higher than the U.S. average ADR but the difference was not statistically significant (48.6% vs. 35.6%, p = 0.08), and the ADR in the German cohort (29.4%) was similar to the national German average risk screening cohort (31.3% in men, p = 0.84; 20.1% in women, p = 0.08). In our screening cohort with CDH1 PV carriers, we demonstrated an ADR of 13.5% in individuals under 45 years, similar to the ADR in patients aged 25-40 years with a family history of CRC. Overall, SSL detection rate was 9.7%. Colorectal cancer was diagnosed in 3 patients (3.2%), 2/3 with an early age of onset before the age of 50 years. This first international study provides preliminary evidence of a higher ADR in U.S. CDH1 PV carriers compared to the general population, with a high number of adenomas detected before the age of 50. This may indicate an increased CRC risk that should be explored in larger studies.
CDH1基因种系（可能的）致病性变异（PV）使携带者易患遗传性弥漫性胃癌和小叶性乳腺癌。美国此前的研究表明，CDH1变异携带者患腺瘤或无蒂锯齿状病变（SSL）的风险增加，但将CDH1 PV与结直肠肿瘤联系起来的数据却很少。我们旨在调查CDH1 PV携带者的结肠镜检查结果。纳入了在2004年1月1日至2023年12月31日期间进行过≥1次结肠镜检查的携带CDH1基因PV/LPV的成年人。患者来自克利夫兰诊所的大卫·G·贾格尔曼遗传性结直肠癌登记处和德国家族性肠道癌联盟。共纳入103名CDH1 PV携带者。大多数为女性（66%），白人（93.1%）。首次结肠镜检查的中位年龄为47岁。德国队列中的腺瘤检出率（ADR）为29.4%（95%CI：19.9 - 41.1%），克利夫兰队列中的腺瘤检出率为48.6%（95%CI：33.0 - 64.4%）（p = 0.055），且与年龄显著相关（<45岁，13.6%（95%CI：6.40 - 26.7%）；45 - 49岁，52.4%（95%CI：32.4 - 71.7%）；≥50岁，52.6%（95%CI：37.3 - 67.5%）；p < 0.001）。克利夫兰队列中的ADR高于美国平均ADR，但差异无统计学意义（48.6%对35.6%，p = 0.08），德国队列中的ADR（29.4%）与德国全国平均风险筛查队列相似（男性为31.3%，p = 0.84；女性为20.1%，p = 0.08）。在我们的CDH1 PV携带者筛查队列中，45岁以下个体的ADR为13.5%，与有结直肠癌家族史的25 - 40岁患者的ADR相似。总体而言，SSL检出率为9.7%。3例患者（3.2%）被诊断为结直肠癌，其中2/3发病年龄早于50岁。这项首次的国际研究提供了初步证据，表明美国CDH1 PV携带者的ADR高于普通人群，且在50岁之前检测到大量腺瘤。这可能表明结直肠癌风险增加，应在更大规模的研究中进行探索。
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