目的:在胰腺癌(PC)患者中常规推荐进行生殖系BRCA1-2测试,由于其临床流行病学相关性。在意大利,未选择的PC病例中,其他癌症易感性和DNA损伤修复(DDR)系统相关基因中种系致病性变异(gPV)的患病率数据很少。我们在多中心队列中评估了这种患病率,为PC患者提供建议。
方法:1200例连续PC患者的临床数据,任何年龄和阶段,收集用多基因种系小组测试的。gPV频率和临床变量的描述性分析在1092名患者中进行了18个基因核心小组(CP-18队列)测试,并在869名仅针对CDKN2A进行了筛查。
结果:11.5%(126/1092)的CP-18队列患者在≥1个基因中携带gPV。在ATM中检测到最高的gPV频率(3.1%),BRCA2(2.9%),BRCA1(1.6%),CHEK2(1.1%)。与无gPV患者相比,携带任何CP-18基因和BRCA1-2gPV的患者更年轻,个人(PH)或癌症家族史(FH)的发生率更高。在所有亚组患者中,gPV的风险≥7%,包括年龄>73岁,肿瘤I-III期且FH/PH阴性的患者。2.6%(23/869)的患者检测到CDKN2AgPV。
结论:据报道,在连续和未选择的PC患者的大型多中心队列中,gPV在癌症易感性和DDR基因中的显着患病率。因此,我们建议多基因种系测试(至少包括BRCA1-2,ATM,CDKN2A,PALB2)适用于所有PC患者,不论年龄,舞台,PH/FH。
OBJECTIVE: Germline BRCA1-2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients.
METHODS: Clinical data of 1200 consecutive PC patients, of any age and stage, tested with a multigene germline panel were collected. A descriptive analysis of gPV frequency and clinical variables was performed both in 1092 patients tested for an 18 genes core-panel (CP-18 cohort) and in 869 patients screened only for CDKN2A.
RESULTS: 11.5 % (126/1092) of CP-18 cohort patients harbored a gPV in ≥ 1 gene. Highest gPV frequencies were detected in ATM (3.1 %), BRCA2 (2.9 %), BRCA1 (1.6 %), CHEK2 (1.1 %). Patients harboring any CP-18 gene and BRCA1-2 gPV were younger and with a higher rate of personal (PH) or family history (FH) of cancer when compared to no gPV patients. The risk of having a gPV was ≥ 7 % in all subgroups of patients, including those aged > 73, with tumor stage I-III and negative FH/PH. CDKN2A gPV were detected in 2.6 % (23/869) of patients.
CONCLUSIONS: A remarkable prevalence of gPV in cancer predisposition and DDR genes is reported in this large multicentre cohort of consecutive and unselected PC patients. Therefore, we recommend multigene germline testing (at least including BRCA1-2, ATM, CDKN2A, PALB2) for all PC patients, irrespective of age, stage, PH/FH.