Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Breast Cancer Res Treat. 2018 Feb;168(1):277-281. doi: 10.1007/s10549-017-4588-7. Epub 2017 Nov 22.
Several common genetic variants (single-nucleotide polymorphisms, SNPs) have been shown to be associated with breast cancer (BC) risk in the general population, and to modify BC risk for BRCA1 and BRCA2 mutation carriers. Co-localization of variable number of tandem repeats (VNTRs) with these BC-associated SNPS has not been comprehensively studied.
Cross referencing of genome-wide VNTRs with the known BC genome-wide association studies (GWAS) SNPs significantly associated with increased risk for developing breast cancer was carried out. Analysis was based on the overlap between the VNTRs and 10-kb windows around these BC-susceptibility SNPs.
Cross referencing of the 1.2 million TR with the 161 known BC-associated SNPs in the general population led to 690 matches. Of those, in 17 VNTRs, the SNP was within the VNTR. Analysis restricted to loci known to modify BC penetrance in BRCA1 (n = 31) and BRCA2 (n = 33) mutation carriers led to 139 and 170 co-localization matches, respectively. For these, none of the SNPs were within the VNTR. The distances between the SNPs and the VNTRs were not significantly different from what was expected to occur by chance alone (p = 0.61; p = 0.44; p = 0.25, respectively).
There is no evidence that VNTRs co-localize with currently reported SNP tagged BC GWAS loci.
多项常见的遗传变异（单核苷酸多态性，SNP）已被证实与普通人群中的乳腺癌（BC）风险相关，并改变了 BRCA1 和 BRCA2 突变携带者的 BC 风险。可变数目的串联重复（VNTRs）与这些与 BC 相关的 SNP 的共定位尚未得到全面研究。
通过基因组范围的 VNTR 与已知与乳腺癌风险增加显著相关的全基因组关联研究（GWAS）SNP 进行交叉引用。分析基于 VNTRs 与这些 BC 易感性 SNP 周围 10kb 窗口之间的重叠。
将 120 万个 TR 与普通人群中 161 个已知的与 BC 相关的 SNP 进行交叉引用，导致 690 个匹配。其中，在 17 个 VNTR 中，SNP 位于 VNTR 内。对已知可改变 BRCA1（n=31）和 BRCA2（n=33）突变携带者 BC 外显率的位点进行分析，分别导致了 139 个和 170 个共定位匹配。对于这些，没有一个 SNP 位于 VNTR 内。SNP 与 VNTR 之间的距离与仅由机会引起的预期没有显著差异（p=0.61；p=0.44；p=0.25，分别）。
没有证据表明 VNTR 与目前报道的 SNP 标记的 BC GWAS 位点共定位。
