BackgroundPancreatic cancer (PC) is an aggressive disease with a dismal 5-year survival rate. Surveillance of high-risk individuals is hoped to improve survival outcomes by detection of precursor lesions or early-stage malignancy.MethodsSince 2011, a national high-risk cohort recruited through St Vincent’s Hospital, Sydney, has undergone prospective PC screening incorporating annual endoscopic ultrasound, formal genetic counselling and mutation analysis as appropriate. PancPRO, a Bayesian PC risk assessment model, was used to estimate 5-year and lifetime PC risks for familial pancreatic cancer (FPC) participants and this was compared to their perceived chance of pancreatic and other cancers. Genetic counselling guidelines were developed to improve consistency. Follow-up questionnaires were used to assess the role of genetic counselling and testing.ResultsWe describe the Australian PC screening program design and recruitment strategy and the results of the first 102 individuals who have completed at least one-year of follow-up. Seventy-nine participants met the FPC criteria (≥ two first-degree relatives affected), 22 individuals had both a BRCA2 pathogenic variant and a close relative with PC and one had a clinical diagnosis of Peutz-Jeghers syndrome. Participants reported a high perceived chance of developing PC regardless of their genetic testing status. PancPRO reported FPC participants’ mean 5-year and lifetime PC risks as 1.81% (range 0.2–3.2%) and 10.17% (range 2.4–14.4%), respectively. Participants’ perceived PC chance did not correlate with their PancPRO 5-year (r = − 0.17, p = 0.128) and lifetime PC risks (r = 0.19, p = 0.091). Two-thirds felt that current genetic testing would help them, and 91% of tested participants were glad to have undergone genetic testing. Overall, 79% of participants found genetic counselling to be helpful, and 88% reported they would recommend counselling to their relatives.ConclusionsParticipants reported multiple benefits of genetic counselling and testing but continue to seek greater clarification about their individual PC risk. Extension of PancPRO is required to enable personalised PC risk assessment for all high-risk sub-groups. More detailed discussion of PC risk for BRCA2 pathogenic variant carriers, providing a written summary in all cases and a plan for genetics review were identified as areas for improvement.

中文翻译：

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澳大利亚胰腺癌筛查项目中的遗传咨询和个性化风险评估

背景胰腺癌 (PC) 是一种侵袭性疾病，5 年生存率低。对高危个体的监测有望通过检测前驱病变或早期恶性肿瘤来改善生存结果。方法自 2011 年以来，通过悉尼圣文森特医院招募的全国高危人群已经接受了前瞻性 PC 筛查，包括每年一次的内窥镜超声检查，适当的正式遗传咨询和突变分析。PancPRO 是一种贝叶斯 PC 风险评估模型，用于估计家族性胰腺癌 (FPC) 参与者的 5 年和终生 PC 风险，并将其与他们感知到的胰腺癌和其他癌症的几率进行比较。制定了遗传咨询指南以提高一致性。后续问卷用于评估遗传咨询和检测的作用。结果我们描述了澳大利亚 PC 筛查项目的设计和招募策略，以及完成至少一年随访的前 102 名个体的结果。79 名参与者符合 FPC 标准（≥ 2 名一级亲属受影响），22 人同时患有 BRCA2 致病性变异和 PC 近亲，1 人临床诊断为 Peutz-Jeghers 综合征。参与者报告说，无论他们的基因检测状态如何，他们患 PC 的可能性都很高。PancPRO 报告 FPC 参与者的平均 5 年和终生 PC 风险分别为 1.81%（范围 0.2-3.2%）和 10.17%（范围 2.4-14.4%）。参与者感知的 PC 机会与他们的 PancPRO 5 年 (r = - 0.17, p = 0.128) 和终生 PC 风险 (r = 0.19, p = 0.091) 无关。三分之二的人认为当前的基因检测会对他们有所帮助，91% 的受测参与者很高兴接受了基因检测。总体而言，79% 的参与者认为遗传咨询很有帮助，88% 的人表示他们会向他们的亲属推荐咨询。结论参与者报告了遗传咨询和检测的多重好处，但继续寻求更多关于他们个人 PC 风险的澄清。需要扩展 PancPRO 才能对所有高风险子组进行个性化 PC 风险评估。更详细地讨论 BRCA2 致病性变异携带者的 PC 风险，提供所有病例的书面总结和遗传学审查计划，被确定为需要改进的领域。79% 的参与者发现遗传咨询很有帮助，88% 的人报告他们会向他们的亲属推荐咨询。结论参与者报告了遗传咨询和检测的多重好处，但继续寻求更多关于他们个人 PC 风险的澄清。需要扩展 PancPRO 才能对所有高风险子组进行个性化 PC 风险评估。更详细地讨论 BRCA2 致病性变异携带者的 PC 风险，提供所有病例的书面总结和遗传学审查计划，被确定为需要改进的领域。79% 的参与者发现遗传咨询很有帮助，88% 的人报告他们会向他们的亲属推荐咨询。结论参与者报告了遗传咨询和检测的多重好处，但继续寻求更多关于他们个人 PC 风险的澄清。需要扩展 PancPRO 才能对所有高风险子组进行个性化 PC 风险评估。更详细地讨论 BRCA2 致病性变异携带者的 PC 风险，提供所有病例的书面总结和遗传学审查计划，被确定为需要改进的领域。需要扩展 PancPRO 才能对所有高风险子组进行个性化 PC 风险评估。更详细地讨论 BRCA2 致病性变异携带者的 PC 风险，提供所有病例的书面总结和遗传学审查计划，被确定为需要改进的领域。需要扩展 PancPRO 才能对所有高风险子组进行个性化 PC 风险评估。更详细地讨论 BRCA2 致病性变异携带者的 PC 风险，提供所有病例的书面总结和遗传学审查计划，被确定为需要改进的领域。