PDF(Pubmed)
Abstract：
BACKGROUND: Familial Pancreatic Cancer (FPC) presents a notable risk, with 3-10% of pancreatic adenocarcinoma cases having a family history. Studies link FPC to syndromes like HBOC, suggesting BRCA1/BRCA2 mutations play a role. BRCA gene functions in DNA repair impact FPC management, influencing sensitivity to therapies like PARP inhibitors. Identifying mutations not only aids FPC treatment but also reveals broader cancer risks. However, challenges persist in selectively applying genetic testing due to cost constraints. This Systematic Review focuses on BRCA1/BRCA2 significance in FPC, diagnostic criteria, prognostic value, and limitations.
METHODS: Original articles published from 2013 to January 2023 were sourced from databases such as Scopus, PubMed, ProQuest, and ScienceDirect. Inclusion criteria comprised observational cohort or diagnostic studies related to the role of BRCA1/2 mutation in correlation to familial pancreatic cancer (FPC), while article reviews, narrative reviews, and non-relevant content were excluded. The assessment of bias used ROBINS-I, and the results were organized using PICOS criteria in a Google spreadsheet table. The systematic review adhered to the PRISMA 2020 checklist.
RESULTS: We analyzed 9 diagnostic studies encompassing 1325 families and 4267 patients from Italy, USA, and Poland. Despite the limitation of limited homogenous PICO studies, our findings effectively present evidence. BRCA1/2 demonstrates benefits in detecting first-degree relatives FPC involvement with 2.26-10 times higher risk. These mutation findings also play an important role since with the BRCA1/2 targeted therapy, Poly-ADP Ribose Polymerase inhibitors (PARP) may give better outcomes of FPC treatment. Analysis of BRCA1 and BRCA2 administration\'s impact on odds ratio (OR) based on six and five studies respectively. BRCA1 exhibited non-significant effects (OR = 1.26, P = 0.51), while BRCA2 showed significance (OR = 1.68, P = 0.04). No heterogeneity observed, indicating consistent results. Further research on BRCA1 is warranted.
CONCLUSIONS: Detecting the BRCA1/2 mutation gene offers numerous advantages, particularly in its correlation with FPC. For diagnostic and prognostic purposes, testing is strongly recommended for first-degree relatives, who face a significantly higher risk (2.26-10 times) of being affected. Additionally, FPC patients with identified BRCA1/2 mutations exhibit a more favorable prognosis compared to the non-mutated population. This is attributed to the availability of targeted BRCA1/2 therapy, which maximizes treatment outcomes.
METHODS: Original articles published from 2013 to January 2023 were sourced from databases such as Scopus, PubMed, ProQuest, and ScienceDirect. Inclusion criteria comprised observational cohort or diagnostic studies related to the role of BRCA1/2 mutation in correlation to familial pancreatic cancer (FPC), while article reviews, narrative reviews, and non-relevant content were excluded. The assessment of bias used ROBINS-I, and the results were organized using PICOS criteria in a Google spreadsheet table. The systematic review adhered to the PRISMA 2020 checklist.
RESULTS: We analyzed 9 diagnostic studies encompassing 1325 families and 4267 patients from Italy, USA, and Poland. Despite the limitation of limited homogenous PICO studies, our findings effectively present evidence. BRCA1/2 demonstrates benefits in detecting first-degree relatives FPC involvement with 2.26-10 times higher risk. These mutation findings also play an important role since with the BRCA1/2 targeted therapy, Poly-ADP Ribose Polymerase inhibitors (PARP) may give better outcomes of FPC treatment. Analysis of BRCA1 and BRCA2 administration\'s impact on odds ratio (OR) based on six and five studies respectively. BRCA1 exhibited non-significant effects (OR = 1.26, P = 0.51), while BRCA2 showed significance (OR = 1.68, P = 0.04). No heterogeneity observed, indicating consistent results. Further research on BRCA1 is warranted.
CONCLUSIONS: Detecting the BRCA1/2 mutation gene offers numerous advantages, particularly in its correlation with FPC. For diagnostic and prognostic purposes, testing is strongly recommended for first-degree relatives, who face a significantly higher risk (2.26-10 times) of being affected. Additionally, FPC patients with identified BRCA1/2 mutations exhibit a more favorable prognosis compared to the non-mutated population. This is attributed to the availability of targeted BRCA1/2 therapy, which maximizes treatment outcomes.
摘要：
背景：家族性胰腺癌（FPC）存在明显的风险，3-10％的胰腺腺癌病例有家族史。研究将FPC与HBOC等综合征联系起来，提示BRCA1/BRCA2突变发挥作用。BRCA基因在DNA修复中的功能影响FPC管理，影响对PARP抑制剂等疗法的敏感性。识别突变不仅有助于FPC治疗，而且还揭示了更广泛的癌症风险。然而,由于成本限制，有选择地应用基因检测仍然存在挑战。这篇系统综述集中于BRCA1/BRCA2在FPC中的意义，诊断标准,预后价值，和限制。
方法：2013年至2023年1月发表的原始文章来自Scopus等数据库，PubMed,ProQuest,和科学直接。纳入标准包括与BRCA1/2突变在家族性胰腺癌（FPC）相关性中的作用相关的观察性队列或诊断性研究。虽然文章评论，叙事评论，不相关的内容被排除。偏见的评估使用ROBINS-I，结果使用Google电子表格中的PICOS标准进行组织。系统审查遵循了PRISMA2020清单。
结果：我们分析了9项诊断研究，包括来自意大利的1325个家庭和4267名患者，美国,和波兰。尽管有限的同质PICO研究受到限制，我们的发现有效地提供了证据.BRCA1/2证明在检测一级亲属FPC参与方面具有2.26-10倍的风险。这些突变发现也起着重要作用，因为BRCA1/2靶向治疗，聚ADP核糖聚合酶抑制剂（PARP）可能会给FPC治疗带来更好的结果。分别基于6项和5项研究分析BRCA1和BRCA2给药对比值比(OR)的影响。BRCA1效应不显著(OR=1.26,P=0.51),BRCA2有显著性差异(OR=1.68,P=0.04)。没有观察到异质性，表明结果一致。有必要对BRCA1进行进一步研究。
结论：检测BRCA1/2突变基因具有许多优点，特别是与FPC的相关性。出于诊断和预后目的，强烈建议对一级亲属进行测试，谁面临显著较高的风险（2.26-10倍）的影响。此外,与未突变的群体相比,具有鉴定的BRCA1/2突变的FPC患者表现出更有利的预后。这归因于靶向BRCA1/2治疗的可用性，最大限度地提高治疗效果。
方法：2013年至2023年1月发表的原始文章来自Scopus等数据库，PubMed,ProQuest,和科学直接。纳入标准包括与BRCA1/2突变在家族性胰腺癌（FPC）相关性中的作用相关的观察性队列或诊断性研究。虽然文章评论，叙事评论，不相关的内容被排除。偏见的评估使用ROBINS-I，结果使用Google电子表格中的PICOS标准进行组织。系统审查遵循了PRISMA2020清单。
结果：我们分析了9项诊断研究，包括来自意大利的1325个家庭和4267名患者，美国,和波兰。尽管有限的同质PICO研究受到限制，我们的发现有效地提供了证据.BRCA1/2证明在检测一级亲属FPC参与方面具有2.26-10倍的风险。这些突变发现也起着重要作用，因为BRCA1/2靶向治疗，聚ADP核糖聚合酶抑制剂（PARP）可能会给FPC治疗带来更好的结果。分别基于6项和5项研究分析BRCA1和BRCA2给药对比值比(OR)的影响。BRCA1效应不显著(OR=1.26,P=0.51),BRCA2有显著性差异(OR=1.68,P=0.04)。没有观察到异质性，表明结果一致。有必要对BRCA1进行进一步研究。
结论：检测BRCA1/2突变基因具有许多优点，特别是与FPC的相关性。出于诊断和预后目的，强烈建议对一级亲属进行测试，谁面临显著较高的风险（2.26-10倍）的影响。此外,与未突变的群体相比,具有鉴定的BRCA1/2突变的FPC患者表现出更有利的预后。这归因于靶向BRCA1/2治疗的可用性，最大限度地提高治疗效果。
