Mak Sau, Alexander James L, Clark Susan K, Hawkins Menna, Cuthill Victoria, Latchford Andrew, Monahan Kevin J
Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Imperial College Healthcare NHS Trust, London, UK.
Clin Transl Gastroenterol. 2024 Jan 1;15(1):e00645. doi: 10.14309/ctg.0000000000000645.
Adenoma multiplicity is associated with increased colorectal cancer (CRC) risk. The utility of genetic testing in patients with multiple colorectal adenomas (MCRA) remains uncertain. We evaluated the diagnostic yield of mutations in polyposis- and CRC-associated genes in patients with MCRA.
We performed a cross-sectional review of adult patients with 10-99 cumulative adenomas from the prospective database at the St Mark's Hospital Polyposis Registry and Family Cancer Clinic between 1999 and 2021. Genetic testing was performed for adenomatous polyposis-associated genes, hamartomatous polyposis-associated genes, and nonpolyposis colorectal cancer-associated genes. Clinicopathological outcomes were extracted for multiple logistic regression analysis.
Two hundred fifty-nine patients with MCRA (median age 61 [interquartile range 53-69] years) were identified. Sixty-six patients (25.5%) had a pathogenic variant or likely pathogenic variant, with APC and biallelic MUTYH mutations constituting the majority of identified pathogenic variant/likely pathogenic variants. Diagnostic yields were greater than 10% at any adenoma burden. In univariate analysis, higher adenoma burden and younger age were associated with higher yield (both P < 0.0001). In patients with MCRA with 10-19 adenomas without a relevant personal or family history of CRC, the diagnostic yield was nil. In multiple logistic regression analysis, higher adenoma burden, younger age, personal history of CRC, and first-degree familial history of CRC were associated with higher diagnostic yield.
Diagnostic yield of >10% at any adenoma burden supports current guidance for constitutional genetic testing in patients with MCRA, although the low yield in people older than 60 years with 10-19 adenomas suggests that a stratified approach might be appropriate.
腺瘤多发性与结直肠癌（CRC）风险增加相关。基因检测在多发性结直肠腺瘤（MCRA）患者中的效用仍不确定。我们评估了MCRA患者中息肉病和CRC相关基因的突变诊断率。
我们对1999年至2021年间圣马克医院息肉病登记处和家庭癌症诊所前瞻性数据库中累积腺瘤数为10 - 99个的成年患者进行了横断面回顾。对腺瘤性息肉病相关基因、错构瘤性息肉病相关基因和非息肉病性结直肠癌相关基因进行了基因检测。提取临床病理结果进行多因素逻辑回归分析。
共识别出259例MCRA患者（中位年龄61岁[四分位间距53 - 69岁]）。66例患者（25.5%）有致病性变异或可能致病性变异，其中APC和双等位基因MUTYH突变构成了已识别致病性变异/可能致病性变异的大部分。在任何腺瘤负担水平下，诊断率均高于10%。单因素分析中，较高的腺瘤负担和较年轻的年龄与较高的诊断率相关（均P < 0.0001）。在无CRC相关个人或家族史的10 - 19个腺瘤的MCRA患者中，诊断率为零。多因素逻辑回归分析中，较高的腺瘤负担、较年轻的年龄、CRC个人史和CRC一级家族史与较高的诊断率相关。
在任何腺瘤负担水平下诊断率>10%支持当前对MCRA患者进行遗传性基因检测的指导意见，尽管60岁以上且有10 - 19个腺瘤的患者诊断率较低，提示分层方法可能合适。
