中国北方汉族人群中 VEGF 单核苷酸多态性与乳腺癌的相关性研究。

Association between VEGF single nucleotide polymorphism and breast cancer in the Northern China Han population.

机构信息

Department of Ultrasound, Second Affiliated Hospital of Harbin Medical University, No 246 XueFu Road, Nan Gang Dist., Harbin, 150086, Heilongjiang Province, China.

Department of General Surgery, Second Hospital of Hebei Medical University, Add: 215 Peace Road, Shijiazhuang, Hebei Province, China.

出版信息

Breast Cancer Res Treat. 2021 Feb;186(1):149-156. doi: 10.1007/s10549-020-06024-3. Epub 2021 Jan 3.

DOI:10.1007/s10549-020-06024-3

PMID:33392836

Abstract

PURPOSE

To investigate the associations of four commonly studied single nucleotide polymorphisms (SNP) of the vascular endothelial growth factor (VEGF), including -460T/C (rs833061), - 634G/C (rs2010963), - 2578C/A (rs699947), and +936T/C (rs3025039), with the incidence, aggressiveness, and tumor markers expression of breast cancer in the Northern China Han population.

METHODS

Followed the genomic DNA extraction, a total of 259 patients with breast cancer (case group) and 273 healthy women (control group) underwent genotyping by PCR-LDR SNP assays. The associations between VEGF gene polymorphisms and the incidence, aggressiveness, and tumor markers expression of breast cancer were analyzed.

RESULTS

Significant differences were observed in allele frequency and genotype distribution of - 634G/C between breast cancer cases and healthy controls (p = 0.006, 0.013). Individuals who carry the G allele more likely had a lower risk of breast cancer (OR, 0.866, 95% CI 0.782-0.959). Compared with CC genotype carriers, women who had the CG and GG genotypes demonstrated a relatively lower risk (OR, 0.860, 95% CI 0.757-0.978, p = 0.022; OR, 0.778, 95% CI, 0.656-0.924, p = 0.004, respectively). When we stratified the group of patients according to the status of tumor markers, a significant association of - 634G/C SNP and Ki-67 expression was observed. The CC genotype carriers were more likely to be characterized by high expression of Ki-67 (p = 0.031). Further analysis showed that the - 460T/-634C/-2578C/+936C haplotype was more associated with a higher risk of breast cancer (OR, 1.445, 95% CI 1.123-1.859, p = 0.004), whereas the - 460T/- 634G/- 2578C/+936C one was associated with a lower risk (OR, 0.736, 95% CI 0.563-0.963, p = 0.025).

CONCLUSIONS

In the present study, we concluded that VEGF gene - 634G/C polymorphism is related to the incidence of breast cancer in the Han population in Northern China and also might be associated with tumor proliferation index Ki-67.

摘要

目的

研究血管内皮生长因子（VEGF）中四个常见单核苷酸多态性（SNP）-460T/C（rs833061）、-634G/C（rs2010963）、-2578C/A（rs699947）和+936T/C（rs3025039）与中国北方汉族人群乳腺癌的发生、侵袭性和肿瘤标志物表达的相关性。

方法

通过基因组 DNA 提取，对 259 例乳腺癌患者（病例组）和 273 例健康女性（对照组）进行聚合酶链反应-连接酶检测反应（PCR-LDR）SNP 分析。分析 VEGF 基因多态性与乳腺癌发生、侵袭性和肿瘤标志物表达的相关性。

结果

乳腺癌患者与健康对照组间-634G/C 等位基因频率和基因型分布存在显著差异（p = 0.006，0.013）。携带 G 等位基因的个体患乳腺癌的风险较低（OR，0.866，95%CI 0.782-0.959）。与 CC 基因型携带者相比，CG 和 GG 基因型携带者的风险相对较低（OR，0.860，95%CI 0.757-0.978，p = 0.022；OR，0.778，95%CI，0.656-0.924，p = 0.004）。当我们根据肿瘤标志物状态对患者进行分层时，-634G/C SNP 与 Ki-67 表达之间存在显著关联。CC 基因型携带者更可能表现为 Ki-67 高表达（p = 0.031）。进一步分析显示，-460T/-634C/-2578C/+936C 单倍型与乳腺癌风险增加更相关（OR，1.445，95%CI 1.123-1.859，p = 0.004），而-460T/-634G/-2578C/+936C 单倍型与乳腺癌风险降低相关（OR，0.736，95%CI 0.563-0.963，p = 0.025）。