拉脱维亚人群中乳腺癌易感基因的等位基因变异

Allelic variants of breast cancer susceptibility genes and in the Latvian population.

作者信息

Hilz Philip, Heinrihsone Reicela, Pätzold Lukas Alexander, Qi Qi, Trofimovics Genadijs, Gailite Linda, Irmejs Arvids, Gardovskis Janis, Miklasevics Edvins, Daneberga Zanda

机构信息

1Institute of Oncology, Riga Stradins University, Dzirciema street 16, Riga, LV-1007 Latvia.

Present address:Center for Anaesthesiology and Intensive Care Medicine, Martinistreet 52, Building Ost 10, 2.OG, 20246 Hamburg, Germany.

出版信息

Hered Cancer Clin Pract. 2019 Jul 3;17:17. doi: 10.1186/s13053-019-0116-6. eCollection 2019.

DOI:10.1186/s13053-019-0116-6

PMID:31312277

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6610821/

Abstract

BACKGROUND

Large-scale case control studies revealed a number of moderate risk - low frequency breast cancer alleles of the and genes. Some of these were reported as founder variants of Central and Eastern Europe. Based on highly similar founder variant spectra of the 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 gene and c.1667_1667+3delAGTA variant of the 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.

METHODS

The 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.

RESULTS

The calculated frequency for c.509_510delGA of the 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; = 0.19). As for the 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; -value = 0.80). There were no carriers of the 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; -value = 0.38).

CONCLUSION

Results obtained for the 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 variant c.1667_1667+3delAGTA allele to breast cancer development.

摘要

背景

大规模病例对照研究揭示了多个BRCA1和BRCA2基因的中度风险——低频乳腺癌等位基因。其中一些被报道为中东欧的始祖变异。基于波兰和拉脱维亚BRCA1高度相似的始祖变异谱，我们决定在拉脱维亚的一个乳腺癌病例对照系列中检测BRCA1基因其他常见的中度乳腺癌风险变异——c.509_510delGA（rs515726124）和c.172_175delTTGT（rs180177143），以及BRCA2基因的c.1667_1667 + 3delAGTA变异，以更好地了解这些基因在乳腺癌易感性中的作用及其临床意义。

方法

病例对照研究基于2480名未经过筛选的乳腺癌女性病例组和一个对照组进行，对照组包括1240名据我们所知无肿瘤疾病报告的自愿女性捐赠者。

结果

病例组中BRCA1基因c.509_510delGA的计算频率为0.35%，对照组为0.00%，相对风险（RR）分别为7.18（95%CI 0.37 - 138.75；P值 = 0.19）。至于BRCA1基因的c.172_175delTTGT变异，我们研究病例组中的频率为0.04%。在我们研究的对照组中，所有个体均为野生型等位基因纯合子，这导致计算出的RR = 1.50（95%CI 0.06 - 36.83；P值 = 0.80）。在我们的病例组中未发现BRCA2基因变异c.1667_1667 + 3delAGTA的携带者，在对照组中鉴定出2名杂合子。计算出的RR = 0.26（95%CI 0.01 - 5.33；P值 = 0.38）。