Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Department of Surgical Oncology and Breast Surgery, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Asian Pac J Cancer Prev. 2022 Apr 1;23(4):1359-1364. doi: 10.31557/APJCP.2022.23.4.1359.
Breast cancer (BC) is one of the major health problems affecting females in Egypt. Certain chromosomal loci abnormalities were proved to be associated with BC in different populations. One of them is chromosomal locus 6q25.1, that affects estrogen receptor gene (ESR) which controls ER receptor expression. Therefore, the aim of this study was to investigate locus 6q25.1 among group of Egyptian female BC patients and compare the results to healthy matched age controls.
Formalin fixed paraffin embedded (FFPE) samples of sixty newly diagnosed BC patients were sequenced for locus 6q25.1 using genetic analyzer with capillary electrophoresis (3500 GA). The identified single nucleotide polymorphisms (SNPs) were compared to blood samples of forty controls. Realtime PCR using TaqMan probes was used for validation.
Two SNPs rs2046210 and rs2046211 were significantly associated with BC. Frequency of rs2046210-A minor allele was 30% in controls, while the frequency of rs2046211-G minor allele was 15%. Rs2046210-A allele was associated with increased risk of BC (P=0.0001), while rs2046211-G allele was associated with reduced risk of BC (P=0.021). Combined analysis of both SNPs showed that haplotype A/C was associated with increased risk of BC (P = 0.042). No significant correlation was found between rs2046210-A allele and ER status, while positive association was observed between rs204621-C allele and ER status (p= 0.005).
Our data confirmed the important association between locus 6q25.1 and risk of BC in other populations. The frequencies of minor alleles of both significant SNPs will pave the way for a wider large-scale genome study and to be investigated with other BC risk factors.
乳腺癌（BC）是影响埃及女性的主要健康问题之一。已经证明，某些染色体位置异常与不同人群中的 BC 有关。其中之一是染色体位置 6q25.1，它影响雌激素受体基因（ESR），控制 ER 受体表达。因此，本研究旨在调查埃及女性 BC 患者群体中的 6q25.1 位置，并将结果与健康匹配年龄的对照组进行比较。
使用带有毛细管电泳（3500GA）的基因分析仪对 60 例新诊断的 BC 患者的福尔马林固定石蜡包埋（FFPE）样本进行 6q25.1 位置测序。将鉴定出的单核苷酸多态性（SNP）与 40 例对照者的血液样本进行比较。使用 TaqMan 探针的实时 PCR 用于验证。
两个 SNP rs2046210 和 rs2046211 与 BC 显著相关。在对照组中，rs2046210-A 次要等位基因的频率为 30%，而 rs2046211-G 次要等位基因的频率为 15%。rs2046210-A 等位基因与 BC 的发病风险增加相关（P=0.0001），而 rs2046211-G 等位基因与 BC 的发病风险降低相关（P=0.021）。对这两个 SNP 的联合分析表明，A/C 单倍型与 BC 的发病风险增加相关（P = 0.042）。rs2046210-A 等位基因与 ER 状态之间未发现显著相关性，而 rs204621-C 等位基因与 ER 状态之间存在正相关（p=0.005）。
我们的数据证实了 6q25.1 位置与其他人群中 BC 风险之间的重要关联。这两个显著 SNP 的次要等位基因的频率将为更广泛的全基因组研究铺平道路，并与其他 BC 风险因素一起进行研究。
