García-Simón Natalia, Valentín Fátima, Royuela Ana, Hidalgo-Calero Beatriz, Blázquez-Martín Ricardo, de-Miguel-Reyes Montserrat, Sánchez-Zapardiel José María, Adán-Merino Luisa, Rodríguez-Festa Alejandro, Gallego-Gil Patricia, Mediavilla-Medel Pilar, Quiñonero-Moreno Laura, Gutiérrez Lourdes, Herreros-de-Tejada Alberto, Sánchez Antonio, Provencio Mariano, Romero Atocha
Hereditary Cancer Unit, Medical Oncology Department, Puerta de Hierro University Hospital, Majadahonda, 28222, Madrid, Spain.
Gastroenterology Department, Biomedical Research Institute (IDIPHISA), Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
Clin Transl Oncol. 2025 Jun;27(6):2710-2718. doi: 10.1007/s12094-024-03811-y. Epub 2024 Dec 11.
APC and MUTYH genes are key in hereditary attenuated adenomatous polyposis syndromes. Guidelines recommend genetic testing based on polyp count, often overlooking age despite its impact on polyp prevalence.
To enhance genetic testing strategies for suspected attenuated adenomatous polyposis by combining polyp count and age in a probability calculator.
Retrospective study of adult patients referred to NGS genetic testing for suspected attenuated adenomatous polyposis (accumulated history of < 100 adenomas) (discovery cohort, N = 138). Data included age, adenoma count, and test results. A multivariable logistic regression model was developed to associate positive genetic test results with age and adenoma count. The model was externally validated with 259 patients from two tertiary hospitals in our region (validation cohort, N = 259).
In the discovery cohort, 13 (9.4%) patients had pathogenic mutations, being younger (OR:0.91, 95%CI 0.86-0.96) and having more adenomas (OR:1.08, 95%CI 1.04-1.13) compared to negative cases. The logistic regression model combining age and polyp count demonstrated an AUC of 0.92. Using a cutoff probability of 3.5%, the model achieved 100% sensitivity and 58% specificity in identifying positive cases. In the external validation, the model accurately predicted 14 out of 16 positive cases (88%). The remaining two positive cases were a patient with an AXIN2 mutation in heterozygosis, and a patient with a NTHL1 mutation in homozygosis. Performance evaluation of both hospitals yielded AUC values of 0.77 and 0.90.
Older individuals with fewer polyps are less likely have hereditary syndromes. Including age in genetic testing criteria can enhance patient selection and cost-effectiveness.
APC和MUTYH基因在遗传性轻度腺瘤性息肉病综合征中起关键作用。指南建议根据息肉数量进行基因检测，尽管年龄对息肉患病率有影响，但常常被忽视。
通过在概率计算器中结合息肉数量和年龄，加强对疑似轻度腺瘤性息肉病的基因检测策略。
对因疑似轻度腺瘤性息肉病（腺瘤累积病史<100个）而接受二代测序基因检测的成年患者进行回顾性研究（发现队列，N = 138）。数据包括年龄、腺瘤数量和检测结果。建立多变量逻辑回归模型，将阳性基因检测结果与年龄和腺瘤数量相关联。该模型在我们地区两家三级医院的259名患者中进行了外部验证（验证队列，N = 259）。
在发现队列中，13名（9.4%）患者有致病突变，与阴性病例相比，年龄更小（比值比：0.91，95%置信区间0.86 - 0.96）且腺瘤更多（比值比：1.08，95%置信区间1.04 - 1.13）。结合年龄和息肉数量的逻辑回归模型的曲线下面积为0.92。使用3.5%的截断概率，该模型在识别阳性病例时灵敏度达到100%，特异性为58%。在外部验证中，该模型准确预测了16例阳性病例中的14例（88%）。其余两例阳性病例分别是一名杂合子AXIN2突变患者和一名纯合子NTHL1突变患者。两家医院的性能评估得出的曲线下面积值分别为0.77和0.90。
息肉较少的老年个体患遗传性综合征的可能性较小。在基因检测标准中纳入年龄可以提高患者选择和成本效益。
