Background The RecQ Like Helicase ( RECQL ) gene has previously been shown to predispose to breast cancer mainly in European populations, in particular to estrogen receptor (ER) and/or progesterone receptor (PR) positive tumor. Here, we investigated the contribution of pathogenic RECQL germline variants to hereditary breast cancer in early-onset and familial breast cancer patients from Pakistan. Methods Comprehensive RECQL variant analysis was performed in 302 BRCA1 and BRCA2 negative patients with ER and/or PR positive breast tumors using denaturing high-performance liquid chromatography followed by DNA sequencing. Novel variants were classified using Sherloc guidelines. Results One novel pathogenic protein-truncating variant (p.W75*) was identified in a 37-year-old familial breast cancer patient. The pathogenic variant frequencies were 0.3% (1/302) in early-onset and familial breast cancer patients and 0.8% (1/133) in familial patients. Further, three novel variants of unknown significance, p.I141F, p.S182S, and p.C475C, were identified in familial breast cancer patients at the age of 47, 68, and 47 respectively. All variants were absent in 250 controls. Conclusions Our data suggest that the RECQL gene plays a negligible role in breast cancer predisposition in Pakistan.

中文翻译：

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巴基斯坦早发性和家族性乳腺癌患者中 RECQL 种系变异的患病率

背景 RecQ Like Helicase (RECQL) 基因先前已被证明主要在欧洲人群中易患乳腺癌，尤其是雌激素受体 (ER) 和/或孕激素受体 (PR) 阳性肿瘤。在这里，我们研究了致病性 RECQL 种系变异对来自巴基斯坦的早发性和家族性乳腺癌患者的遗传性乳腺癌的贡献。方法 使用变性高效液相色谱和 DNA 测序对 302 名 BRCA1 和 BRCA2 阴性的 ER 和/或 PR 阳性乳腺肿瘤患者进行全面的 RECQL 变异分析。使用 Sherloc 指南对新变种进行分类。结果 在一名 37 岁的家族性乳腺癌患者中发现了一种新的致病性蛋白质截短变异 (p.W75*)。致病变异频率为0。在早发性和家族性乳腺癌患者中为 3% (1/302)，在家族性患者中为 0.8% (1/133)。此外，分别在 47、68 和 47 岁的家族性乳腺癌患者中发现了三种意义不明的新变体，p.I141F、p.S182S 和 p.C475C。250 个对照中不存在所有变体。结论 我们的数据表明 RECQL 基因在巴基斯坦乳腺癌易感性中的作用可以忽略不计。