Howard University, Department of Microbiology, Washington, DC, USA.
MedStar Georgetown University Hospital, Pre/Postoperative Services, Washington, DC, USA.
Gene. 2024 Nov 15;927:148695. doi: 10.1016/j.gene.2024.148695. Epub 2024 Jun 28.
Breast cancer (BCa) is a prevalent form of cancer in women, exhibiting varying rates and distribution across different ethnic groups. Among these groups, African American (AA) women have the highest incidence of BCa and the lowest levels of Vitamin D (VD). Numerous studies have explored the connection between variations in the VDR gene and BCa risk, particularly in different populations, but research on the AA population remains limited. Epigenetic modifications, including specific microRNAs (miRNAs), can influence gene expression without altering the genetic code and have been implicated in cancer initiation and progression. Our hypothesis suggests that VDR gene variations may increase BCa risk in AA women and that changes in miRNA expression profiles could contribute to BCa development. Using data from the 1000 Genome Project, we identified five VDR gene variants with significant frequency differences between AA and European-American (EA) populations. We genotyped 404 African American BCa cases and controls for five variants using TaqMan® assays. SNPstats assessed their association with BCa risk. The rs1544410 variant's recessive model (A/A) showed a decreased BCa risk in AA (odds ratio 0.33, 95% CI: 0.15-0.73, p-value 0.0041). Conversely, the rs2853563 variant's recessive model (A/A) was linked to an increased BCa risk (odds ratio 4.04, 95% CI: 1.49-10.95, p-value 0.0022). We investigated miRNA expression influenced by VD in HCC1806 Triple-Negative Breast Cancer (TNBC) cell lines with the A/A allele for rs2853563. nCounter® Nanostring technology assessed miRNA profiles after calcitriol treatment. Our results indicated that calcitriol treatment led to reduced expression of six miRNAs, four of which are associated with tumor suppression in the presence of the AA genotype in TNBC cell lines. These findings suggest that specific VDR genotypes could have a potential effect on the miRNAs expression which could potentially serve as markers for cell proliferation in TNBC.
乳腺癌（BCa）是女性中常见的癌症形式，在不同种族群体中的发病率和分布情况各不相同。在这些群体中，非裔美国（AA）女性的 BCa 发病率最高，维生素 D（VD）水平最低。许多研究都探讨了 VDR 基因变异与 BCa 风险之间的关系，特别是在不同人群中，但针对 AA 人群的研究仍然有限。表观遗传修饰，包括特定的 microRNAs（miRNAs），可以在不改变遗传密码的情况下影响基因表达，并与癌症的发生和发展有关。我们的假设表明，VDR 基因变异可能会增加 AA 女性的 BCa 风险，而 miRNA 表达谱的变化可能会导致 BCa 的发展。我们使用 1000 基因组计划的数据，确定了五个在 AA 和欧洲裔美国人（EA）人群中具有显著频率差异的 VDR 基因变体。我们使用 TaqMan®测定法对 404 例非裔美国 BCa 病例和对照进行了五个变体的基因分型。SNPstats 评估了它们与 BCa 风险的关联。rs1544410 变体的隐性模型（A/A）显示 AA 中 BCa 风险降低（比值比 0.33，95%置信区间：0.15-0.73，p 值 0.0041）。相反，rs2853563 变体的隐性模型（A/A）与 BCa 风险增加相关（比值比 4.04，95%置信区间：1.49-10.95，p 值 0.0022）。我们在具有 rs2853563 等位基因 A/A 的 HCC1806 三阴性乳腺癌（TNBC）细胞系中研究了 VD 影响的 miRNA 表达。nCounter®Nanostring 技术评估了钙三醇处理后的 miRNA 谱。我们的结果表明，钙三醇处理导致 6 种 miRNA 的表达降低，其中 4 种 miRNA 在 TNBC 细胞系中存在 AA 基因型时与肿瘤抑制有关。这些发现表明，特定的 VDR 基因型可能对 miRNA 表达有潜在影响，这可能成为 TNBC 细胞增殖的标志物。
