Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States of America.
Medical Affairs, Invitae Corporation, San Francisco, California, United States of America.
PLoS One. 2024 Aug 22;19(8):e0307076. doi: 10.1371/journal.pone.0307076. eCollection 2024.
BACKGROUND/OBJECTIVES: Germline genetic testing is recommended for younger patients with idiopathic pancreatitis but there has been a lack of consensus in recommendations for those over age 35. We aimed to analyze the results of genetic testing among subjects of varying ages.
Individuals who underwent germline multigene testing for pancreatitis susceptibility genes (CASR, CFTR, CPA1, CTRC, PRSS1, SPINK1) through a large commercial laboratory between 2017 and 2022 were included. Test results and information collected from test requisition forms were evaluated. Multivariable logistic regression models were performed to identify factors associated with a positive pancreatitis panel (pathogenic, likely pathogenic, and/or increased risk variants) in pancreatitis-related genes.
Overall, 2,468 subjects with primary indication of acute pancreatitis (AP) (n = 401), chronic pancreatitis (CP) (n = 631), pancreatic cancer (n = 128), or other indications (n = 1,308) completed germline testing. Among patients with AP or CP, the prevalence of any positive result for those <35 versus ≥35 years of age was 32.1% and 24.5% (p = 0.007), and the prevalence of a clinically meaningful result was 10.8% and 5.4%, respectively (p = 0.001). Positive family history of pancreatitis was associated with increased odds ratio (OR) of 8.59 (95% confidence interval (CI) 2.92-25.25) for a clinically significant panel result while each 5-year increase in age at test completion had lower odds (OR 0.89, 95% CI 0.83-0.95).
The highest prevalence of pathogenic variants is seen in younger individuals with a positive family history of pancreatitis. However, clinically meaningful results are identified in older subjects, suggesting that genetic counseling and testing should be considered for all age groups.
背景/目的：对于特发性胰腺炎的年轻患者，推荐进行种系遗传检测，但对于年龄超过 35 岁的患者，推荐意见尚未达成共识。我们旨在分析不同年龄段患者的基因检测结果。
本研究纳入了 2017 年至 2022 年期间通过一家大型商业实验室进行胰腺炎易感性基因（CASR、CFTR、CPA1、CTRC、PRSS1、SPINK1）种系多基因检测的个体。评估了检测申请单上的检测结果和收集的信息。采用多变量逻辑回归模型，确定与胰腺炎相关基因中胰腺炎面板（致病性、可能致病性和/或增加风险的变异体）阳性相关的因素。
总体而言，共有 2468 名有急性胰腺炎（AP）（n = 401）、慢性胰腺炎（CP）（n = 631）、胰腺癌（n = 128）或其他指征（n = 1308）的个体完成了种系检测。在 AP 或 CP 患者中，<35 岁与≥35 岁患者任何阳性结果的发生率分别为 32.1%和 24.5%（p = 0.007），有临床意义的结果发生率分别为 10.8%和 5.4%（p = 0.001）。阳性胰腺炎家族史与临床显著面板结果的比值比（OR）增加 8.59 倍（95%置信区间 [CI] 2.92-25.25），而每次检测完成时年龄增加 5 岁，OR 降低 0.89（95% CI 0.83-0.95）。
阳性胰腺炎家族史的年轻个体中致病性变异体的发生率最高。然而，在年龄较大的患者中也确定了有临床意义的结果，这表明应考虑为所有年龄段的患者提供遗传咨询和检测。
