Omega-3 or n-3 polyunsaturated fatty acids (PUFAs) are widely studied for health benefits that may relate to anti-inflammatory activity. However, mechanisms mediating an anti-inflammatory response to n-3 PUFA intake are not fully understood. Of interest is the emerging role of fatty acids to impact DNA methylation (DNAm) and thereby modulate mediating inflammatory processes. In this pilot study, we investigated the impact of n-3 PUFA intake on DNAm in inflammation-related signaling pathways in peripheral blood mononuclear cells (PBMCs) of women at high risk of breast cancer.

PBMCs of women at high risk of breast cancer (n=10) were obtained at baseline and after 6 months of n-3 PUFA (5 g/d EPA+DHA dose arm) intake in a previously reported dose finding trial. DNA methylation of PBMCs was assayed by reduced representation bisulfite sequencing (RRBS) to obtain genome-wide methylation profiles at the single nucleotide level. We examined the impact of n-3 PUFA on genome-wide DNAm and focused upon a set of candidate genes associated with inflammation signaling pathways and breast cancer.

We identified 24,842 differentially methylated CpGs (DMCs) in gene promoters of 5507 genes showing significant enrichment for hypermethylation in both the candidate gene and genome-wide analyses. Pathway analysis identified significantly hypermethylated signaling networks after n-3 PUFA treatment, such as the Toll-like Receptor inflammatory pathway. The DNAm pattern in individuals and the response to n-3 PUFA intake are heterogeneous. PBMC DNAm profiling suggests a mechanism whereby n-3 PUFAs may impact inflammatory cascades associated with disease processes including carcinogenesis.

Omega-3 或 n-3 多不饱和脂肪酸 (PUFA) 因可能与抗炎活性有关的健康益处而被广泛研究。然而，介导对 n-3 多不饱和脂肪酸摄入的抗炎反应的机制尚不完全清楚。有趣的是脂肪酸影响 DNA 甲基化 (DNAm) 并从而调节介导的炎症过程的新作用。在这项初步研究中，我们调查了 n-3 PUFA 摄入量对乳腺癌高危女性外周血单核细胞 (PBMC) 炎症相关信号通路中 DNAm 的影响。

在先前报告的剂量探索试验中，在基线时和摄入 n-3 PUFA（5 g/d EPA+DHA 剂量组）6 个月后，获得了乳腺癌高危女性 (n=10) 的 PBMC。通过还原代表性亚硫酸氢盐测序 (RRBS) 测定 PBMC 的 DNA 甲基化，以获得单核苷酸水平的全基因组甲基化谱。我们检查了 n-3 PUFA 对全基因组 DNAm 的影响，并重点关注了一组与炎症信号通路和乳腺癌相关的候选基因。

我们在 5507 个基因的基因启动子中鉴定了 24,842 个差异甲基化的 CpG (DMC)，这些基因在候选基因和全基因组分析中都显示出显着的高甲基化富集。通路分析发现在 n-3 PUFA 处理后显着超甲基化的信号网络，例如 Toll 样受体炎症通路。个体的 DNAm 模式和对 n-3 PUFA 摄入的反应是异质的。PBMC DNAm 分析表明，n-3 PUFA 可能会影响与疾病过程（包括癌变）相关的炎症级联反应。