BackgroundLarge-scale case control studies revealed a number of moderate risk - low frequency breast cancer alleles of the PALB2 and RECQL genes. Some of these were reported as founder variants of Central and Eastern Europe. Based on highly similar founder variant spectra of the BRCA1 in Poland and Latvia, we decided to test the frequency of other common variants of moderate breast cancer risk — c.509_510delGA (rs515726124) and c.172_175delTTGT (rs180177143) of the PALB2 gene and c.1667_1667+3delAGTA variant of the RECQL gene in a breast cancer case-control series from Latvia to better understand the role of genes in susceptibility to breast cancer and their clinical significance.MethodsThe case-control study was performed based on an unselected breast cancer case group of 2480 women and a control group, including 1240 voluntary, to our knowledge unrelated, female donors without reported oncological disease.ResultsThe calculated frequency for c.509_510delGA of the PALB2 gene in the case group is 0.35 and 0.00% in the control group, with respective relative risk (RR) 7.18 (CI 95% 0.37–138.75; p = 0.19). As for the PALB2 c.172_175delTTGT variant, the frequency in the case group of our study is 0.04%. In the control group of our study all individuals were homozygous for the wild-type allele, which lead to calculated RR = 1.50 (CI 95% 0.06–36.83; p-value = 0.80). There were no carriers of the RECQL variant c.1667_1667+3delAGTA identified in our case group and 2 heterozygotes were identified in the control group. The calculated RR = 0.26 (CI 95% 0.01–5.33; p-value = 0.38).ConclusionResults obtained for the PALB2 gene variants are able to supplement evidence on the allele frequency in breast cancer patients from the region of Central and Eastern Europe. Based on our results we cannot confirm the contribution of the RECQL variant c.1667_1667+3delAGTA allele to breast cancer development.

中文翻译：

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拉脱维亚人群中乳腺癌易感基因 PALB2 和 RECQL 的等位变体

背景大规模病例对照研究揭示了 PALB2 和 RECQL 基因的一些中等风险 - 低频乳腺癌等位基因。其中一些被报道为中欧和东欧的创始变体。基于波兰和拉脱维亚 BRCA1 的高度相似的创始人变异谱，我们决定测试其他常见的中度乳腺癌风险变异的频率 - PALB2 基因的 c.509_510delGA (rs515726124) 和 c.172_175delTTGT (rs180177143) 和 c .1667_1667+3delAGTA 变异的 RECQL 基因在来自拉脱维亚的乳腺癌病例对照系列中，以更好地了解基因在乳腺癌易感性中的作用及其临床意义。方法基于未选择的乳腺癌病例进行病例对照研究2480 名女性和一个对照组，其中 1240 名自愿参加，据我们所知，未报告肿瘤疾病的不相关的女性供体。结果病例组中 PALB2 基因 c.509_510delGA 的计算频率为 0.35%，对照组为 0.00%，各自的相对风险 (RR) 为 7.18 (CI 95% 0.37 –138.75；p = 0.19）。至于 PALB2 c.172_175delTTGT 变体，我们研究的病例组中的频率为 0.04%。在我们研究的对照组中，所有个体都是野生型等位基因的纯合子，这导致计算的 RR = 1.50 (CI 95% 0.06–36.83; p 值 = 0.80)。在我们的病例组中没有发现 RECQL 变体 c.1667_1667+3delAGTA 的携带者，在对照组中发现了 2 个杂合子。计算的 RR = 0.26（CI 95% 0.01–5.33；p 值 = 0.38）。结论 PALB2 基因变异的结果能够补充中东欧地区乳腺癌患者等位基因频率的证据。根据我们的结果，我们无法确认 RECQL 变体 c.1667_1667+3delAGTA 等位基因对乳腺癌发展的贡献。