Patel Nikita J, Chen Qiaoling, Luong Tiffany Q, Wu Bechien U
Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California, USA.
Kaiser Permanente Southern California, Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, California, USA.
Clin Transl Gastroenterol. 2025 May 27. doi: 10.14309/ctg.0000000000000857.
Screening guidelines for pancreatic cancer (PC) based on genetic risk do not include patients with cystic fibrosis (CF) or cystic fibrosis transmembrane conductance regulator (CFTR) gene variants. The objective of this study was to determine risk of PC in patients with CF or CFTR pathogenic/likely pathogenic gene variants.
We conducted a retrospective cohort study of CF/CFTR pathogenic/likely pathogenic variants patients in an integrated healthcare system from 2008 to 2023. Index date was the initial encounter within the health system, with censoring at loss of membership, death, or study completion. PC incidence rate was based on person-time at risk. Age-adjusted and sex-adjusted standardized incidence rate ratio (SIR) for PC was calculated for CF/CFTR compared with the non-CFTR reference population. We further stratified PC risk by age and family history of PC.
A total of 12,682 patients with CF/CFTR were included with a median follow-up of 8.3 years (interquartile range 4.3-13.1). The cohort was 88% female, had median age at index of 25.8 (interquartile range 19.1-31.1) years, and was majority White and Hispanic. Eight total PC events occurred in the CF/CFTR group (incidence rate 7.3 per 100,000 person-years). The adjusted SIR for PC was 2.3 (95% confidence interval 1.2-4.7) for CF/CFTR variant patients. There was effect modification by age, with SIR (age ≥50 years) of 2.87 (95% confidence interval 1.37-6.01). Among CF/CFTR patients with family history of PC, 1 PC case was observed with SIR (age ≥50 years) of 13.
Patients with CF or CFTR gene variants had an almost 3-fold higher adjusted risk of PC than the general population after the age of 50 years. The risk may be further increased with a family history of PC.
基于遗传风险的胰腺癌（PC）筛查指南未涵盖囊性纤维化（CF）患者或携带囊性纤维化跨膜传导调节因子（CFTR）基因变异的患者。本研究的目的是确定CF患者或携带CFTR致病/可能致病基因变异的患者患PC的风险。
我们对2008年至2023年综合医疗保健系统中携带CF/CFTR致病/可能致病变异的患者进行了一项回顾性队列研究。索引日期为在医疗系统中的首次就诊时间，以成员资格丧失、死亡或研究结束为截尾。PC发病率基于风险人时。计算了CF/CFTR患者与非CFTR参考人群相比的PC年龄调整和性别调整标准化发病率比（SIR）。我们还按年龄和PC家族史对PC风险进行了分层。
共纳入12682例CF/CFTR患者，中位随访时间为8.3年（四分位间距4.3 - 13.1年）。该队列中88%为女性，索引时的中位年龄为25.8岁（四分位间距19.1 - 31.1岁），大多数为白人和西班牙裔。CF/CFTR组共发生8例PC事件（发病率为每100,000人年7.3例）。CF/CFTR变异患者的PC调整SIR为2.3（95%置信区间1.2 - 4.7）。存在年龄效应修正，年龄≥50岁的SIR为2.87（95%置信区间1.37 - 6.01）。在有PC家族史CF/CFTR患者中，观察到1例PC病例，年龄≥50岁的SIR为13。
CF患者或携带CFTR基因变异的患者在50岁以后患PC的调整风险比一般人群高近3倍。有PC家族史时，风险可能会进一步增加。
