Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
J Natl Cancer Inst. 2022 Dec 8;114(12):1681-1688. doi: 10.1093/jnci/djac167.
A family history of pancreatic cancer is associated with increased pancreatic cancer risk. However, risk estimates for individuals in kindreds with an aggregation of pancreatic cancer (>1 relative) are imprecise because of small samples sizes or potentially impacted by biases inherent in retrospective data.
The objective of this study is to determine the age-specific pancreatic cancer risk as a function of family history using prospective data.
We compared pancreatic cancer incidence (n = 167) in 21 141 individuals from 4433 families enrolled in the National Familial Pancreatic Cancer Registry with that expected based on Surveillance Epidemiology and End Results data and estimated the cumulative probability of pancreatic cancer using competing risk regression.
Familial pancreatic kindred members (kindreds with pancreatic cancer in 2 first-degree relatives [FDRs] or a pathogenic variant) had a standardized incidence ratio of 4.86 (95% confidence interval [CI] = 4.01 to 5.90), and sporadic kindred members (kindreds not meeting familial criteria) had a standardized incidence ratio of 2.55 (95% CI = 1.95 to 3.34). Risk in familial pancreatic cancer kindreds increased with an increasing number of FDRs with pancreatic cancer, with a standardized incidence ratio of 3.46 (95% CI = 2.52 to 4.76), 5.44 (95% CI = 4.07 to 7.26), and 10.78 (95% CI = 6.87 to 16.89) for 1, 2, and 3 or more FDRs with pancreatic cancer, respectively. Risk was also higher among individuals with a family history of young-onset (aged younger than 50 years) pancreatic cancer.
Pancreatic cancer risk is strongly dependent on family history, including both the degree of relationship(s) and age of onset of pancreatic cancer in relatives. These risk estimates will help inform the design of early detection studies and the risk and benefit analysis of screening trials.
胰腺癌家族史与胰腺癌风险增加相关。然而，由于样本量小或受回顾性数据固有偏差的影响，对于家族中有多个胰腺癌患者（≥1 名一级亲属）的个体，风险估计并不准确。
本研究旨在使用前瞻性数据确定家族史与年龄相关的胰腺癌风险。
我们比较了纳入国家家族性胰腺癌登记处的 4433 个家族的 21141 名个体中（n=167）的胰腺癌发病率与基于监测、流行病学和最终结果数据的预期发病率，并使用竞争风险回归估计胰腺癌的累积概率。
家族性胰腺癌家系成员（有 2 名一级亲属[FDR]或致病性变异的家系）的标准化发病率比为 4.86（95%置信区间[CI] = 4.01 至 5.90），散发性家系成员（不符合家族性标准的家系）的标准化发病率比为 2.55（95% CI = 1.95 至 3.34）。家族性胰腺癌家系的风险随着 FDR 胰腺癌数量的增加而增加，标准化发病率比分别为 3.46（95% CI = 2.52 至 4.76）、5.44（95% CI = 4.07 至 7.26）和 10.78（95% CI = 6.87 至 16.89），用于 1、2 和 3 个或更多 FDR 患有胰腺癌。具有早发性（年龄小于 50 岁）胰腺癌家族史的个体风险也更高。
胰腺癌风险与家族史密切相关，包括亲属关系的程度和胰腺癌发病年龄。这些风险估计将有助于为早期检测研究的设计以及筛查试验的风险和获益分析提供信息。
