Dietary walnut altered gene expressions related to tumor growth, survival, and metastasis in breast cancer patients: a pilot clinical trial

Abstract

Consumption of walnuts has slowed breast cancer growth and/or reduced the risk of mammary cancer in mice. The benefit against cancer was associated with altered expression of genes for cancer growth and survival. We hypothesized that walnut consumption would alter gene expression in pathologically confirmed breast cancers of women in a direction that would be expected to decrease breast cancer growth and survival, as was seen in mice. The study was a nonplacebo, 2-arm, clinical trial. Women with breast lumps large enough for research and pathology biopsies were recruited and randomized to walnut consuming or control groups. Immediately after biopsy collection, women in the walnut group began to consume 2 oz of walnuts per day until follow-up surgery. Pathological studies confirmed that lumps were breast cancer in all women who remained in the trial. At surgery, about 2 weeks after biopsy, additional specimens were taken from the breast cancers. Changes in gene expression in the surgical specimen compared to baseline were determined in each individual woman in walnut-consuming (n = 5) and control (n = 5) groups. RNA sequencing expression profiling revealed that expression of 456 identified genes was significantly changed in the tumor due to walnut consumption. Ingenuity Pathway Analysis showed activation of pathways that promote apoptosis and cell adhesion, and inhibition of pathways that promote cell proliferation and migration. These results support the hypothesis that, in humans, walnut consumption could suppress growth and survival of breast cancers.

Dietary Phenolics against Breast Cancer. A Critical Evidence-Based Review and Future Perspectives

“…These authors conducted a pre-surgery trial in 10 BC patients that consumed around 30 g walnuts/day for 15 days (between tumour biopsy and resection). Surprisingly, with only 10 patients, and taking into account the huge inter-individual variability in gene expression and the previously reported artefacts [140,141], they observed the activation of genes participating in pathways that promote apoptosis and cell adhesion and inhibition of pathways that promote cell proliferation and migration (involving 456 genes in the tumour) due to walnut consumption [138]. Recently, Martínez et al described the anti-inflammatory effect (decrease of plasma CRP vs. placebo) in BC patients with no active disease, and receiving adjuvant hormonal therapy, after consuming a mixture containing 460 mg fish oil (EPA, DHA), olive extract (125 mg hydroxytyrosol) and 50 mg curcumin extract for 30 days [139].…”

“…However, they did not observe any effect on NO, IGF-1, and Ki-67 in 12 patients with ER+ breast cancer after consuming 2.8 g/day of a silybin-containing milk thistle extract in combination with phosphatidylcholine for 4 weeks between biopsy diagnosis and resection [65]. The only study dealing with food and BC has been conducted so far by Hardman et al [138]. These authors conducted a pre-surgery trial in 10 BC patients that consumed around 30 g walnuts/day for 15 days (between tumour biopsy and resection).…”

“…Other trials with BC patients and phenolics or phenolic-containing products, included the assay of grapeseed [136], milk thistle [65], and red clover [137] extracts, walnuts [138], and also a product containing a mixture of EPA, DHA hydroxytyrosol and curcumin [139]. In one of the pioneer studies dealing with polyphenols and BC, Brooker et al did not find any effect on tissue hardness due to RT in 69 BC patients after consuming a grapeseed proanthocyanidins extract (300 mg/day) for 12 months vs. placebo [136].…”

Effects of walnut oil on metabolic profile and transcription factors in rats fed high‐carbohydrate‐/‐fat diets

“…Since the adverse effects of synthetic compounds have emerged in recent years, the clinical importance and potential use of natural sources and edible herbal remedies such as antioxidant and antimicrobial effective walnut are increasing even more (Atanasov et al, 2015;Oliveira et al, 2008). Walnuts are comprised of many components including omega-3 fatty acids, phytosterols, β-sitosterol, and antioxidants that were reported to decrease the cancer risk or growth rate and alter the gene expressions in the breast cancer patients (Hardman, Ion, Akinsete, & Witte, 2011;Hardman et al, 2019).…”

mRNA expression data in breast cancers before and after consumption of walnut by women

“…mRNA was extracted from each individual specimen then genome wide mRNA was determined in each specimen via next-generation sequencing. Gene expression ratios were calculated for each gene as: (walnut surgery/walnut biopsy)/(control surgery/control biopsy) for further analyses [1] .…”