1 Johns Hopkins Medical Institutions, Baltimore, MD.
J Clin Oncol. 2019 May 1;37(13):1070-1080. doi: 10.1200/JCO.18.01512. Epub 2019 Mar 18.
To compare the risk of neoplastic progression by germline mutation status versus family history without a known germline mutation (familial risk) among individuals with an increased risk for pancreatic cancer who are undergoing surveillance.
Of 464 high-risk individuals in the Cancer of the Pancreas Screening program at Johns Hopkins Hospital who were undergoing pancreatic surveillance, 119 had a known deleterious germline mutation in a pancreatic cancer susceptibility gene; 345 met family history criteria for pancreatic surveillance but were not known to harbor a germline mutation. We used next-generation sequencing to identify previously unrecognized germline mutations among these 345 individuals. We compared the development of pancreatic cancer, high-grade dysplasia, or clinically worrisome features, adjusting for competing mortality, among all germline mutation carriers with the risk of progression in a cohort without a known germline mutation.
Fifteen (4.3%) of 345 individuals classified as having familial risk had a previously unrecognized pancreatic cancer susceptibility gene mutation (nine that involved , two , one , one , one , and one ). The cumulative incidence of pancreatic cancer, high-grade dysplasia, or worrisome features on pancreatic imaging was significantly higher in the germline mutation risk group (n = 134) than in the familial risk group (n = 330 [for pancreatic cancer, hazard ratio, 2.85; 95% CI, 1.0 to 8.18; = .05]).
The cumulative incidence of pancreatic cancer is significantly higher among individuals with an identifiable deleterious germline mutation in a pancreatic cancer susceptibility gene than it is among individuals with a strong family history but no identified mutation. Gene testing of individuals who meet criteria for pancreatic surveillance on the basis of their family history may better define those most at risk for neoplastic progression.
比较在接受胰腺癌监测的个体中，基于种系突变状态与无已知种系突变的家族史（家族风险）的肿瘤进展风险。
在约翰霍普金斯医院癌症胰腺筛查计划中，464 名高危个体正在接受胰腺监测，其中 119 人携带已知的胰腺癌易感性基因的有害种系突变；345 人符合家族史进行胰腺监测的标准，但不携带种系突变。我们使用下一代测序技术在这 345 名个体中识别以前未被识别的种系突变。我们比较了所有种系突变携带者的胰腺癌、高级别发育不良或临床上令人担忧的特征的发展情况，并调整了竞争死亡率，与一个未知种系突变的队列中的进展风险进行比较。
345 名被归类为具有家族风险的个体中，有 15 名（4.3%）具有先前未被识别的胰腺癌易感性基因突变（涉及 9 个、2 个、1 个、1 个、1 个和 1 个）。在种系突变风险组（n=134）中，胰腺癌、高级别发育不良或胰腺影像学上令人担忧的特征的累积发生率明显高于家族风险组（n=330[胰腺癌的危险比，2.85；95%CI，1.0 至 8.18；=0.05]）。
与具有明确可识别的胰腺癌易感性基因突变的个体相比，具有强烈家族史但未发现突变的个体的胰腺癌累积发生率明显更高。基于家族史符合胰腺监测标准的个体进行基因检测，可能会更好地确定那些最有可能发生肿瘤进展的个体。
