BRCA1 和 BRCA2 (BRCA1/2) 是白种人胰腺癌患者中最常研究的基因，而亚洲人中的报道有限。我们的目的是调查巴基斯坦胰腺癌患者中 BRCA1/2 种系变异的患病率。使用变性高效液相色谱和高分辨率熔解技术对 150 名未经选择和前瞻性入组的胰腺癌患者进行了 BRCA1/2 种系变异的全面筛查分析，然后对变异片段进行 DNA 测序。使用计算机工具分析了新变体的致病作用。在 200 个无癌对照中进一步筛选了潜在的功能变异。仅在 BRCA2 中检测到蛋白质截短变异，患病率为 0.7% (1/150)。在一名有腹部癌家族史的 71 岁帕坦族男性患者中发现了移码 BRCA2 变异 (p.Asp946Ilefs*14)。此外，我们在 BRCA2 (p.Glu2650Gln) 中发现了一个新的变异，在 BRCA1 (p.Thr293Ser) 和 BRCA2 (p.Ile2296Leu) 中发现了两个先前报道的变异，以及在 BRCA2 (p.Lys3326Ter) 中反复出现的无义变异。这些变异被归类为意义不确定的变异（VUS）。值得注意的是，这些 VUS 携带者都没有胰腺癌或其他癌症的家族史。 在第一项研究中，在来自巴基斯坦的胰腺癌患者中发现 BRCA1/2 致病性变异的频率较低。建议对巴基斯坦胰腺癌患者进行全面的多基因小组测试，以增强对该人群的遗传了解。© 2023。作者。

BRCA1 and BRCA2 (BRCA1/2) are the most frequently investigated genes among Caucasian pancreatic cancer patients, whereas limited reports are available among Asians. We aimed to investigate the prevalence of BRCA1/2 germline variants in Pakistani pancreatic cancer patients.One hundred and fifty unselected and prospectively enrolled pancreatic cancer patients were comprehensively screened for BRCA1/2 germline variants using denaturing high-performance liquid chromatography and high-resolution melting analyses, followed by DNA sequencing of the variant fragments. The novel variants were analyzed for their pathogenic effect using in-silico tools. Potentially functional variants were further screened in 200 cancer-free controls.Protein truncating variant was detected in BRCA2 only, with a prevalence of 0.7% (1/150). A frameshift BRCA2 variant (p.Asp946Ilefs*14) was identified in a 71-year-old male patient of Pathan ethnicity, with a family history of abdominal cancer. Additionally, we found a novel variant in BRCA2 (p.Glu2650Gln), two previously reported variants in BRCA1 (p.Thr293Ser) and BRCA2 (p.Ile2296Leu) and a recurrent nonsense variant in BRCA2 (p.Lys3326Ter). These variants were classified as variants of uncertain significance (VUS). It is noteworthy that none of these VUS carriers had a family history of pancreatic or other cancers.In this first study, BRCA1/2 pathogenic variant is identified with a low frequency in pancreatic cancer patients from Pakistan. Comprehensive multigene panel testing is recommended in the Pakistani pancreatic cancer patients to enhance genetic understanding in this population.© 2023. The Author(s).