Abstract
BackgroundHigh protein intake may promote angiogenesis giving support to the development of metastasis according to the experimental data. However, nutritional epidemiologic evidence is inconsistent with metastasis. Therefore, we aimed to study the association between dietary intake of protein and tumoral expression levels of Ras homologous gene family member A (RhoA), vascular endothelial growth factor-A (VEGF-A), and VEGF receptor-2 (VEGFR2) in primary breast cancer (BC) patients.MethodsOver this consecutive case series, 177 women primary diagnosed with histopathologically confirmed BC in Tabriz (Iran) were enrolled between May 2011 and November 2016. A validated food frequency questionnaire was completed for eligible participants. Fold change in gene expression was measured using quantitative real-time PCR. Principal component factor analysis (PCA) was used to express dietary groups of proteins.ResultsTotal protein intake was associated with the expression level of VEGF-A in progesterone receptor-positive (PR+: β = 0.296, p < 0.01) and VEGFR2 in patients with involvement of axillary lymph node metastasis (ALNM+: β = 0.295, p < 0.01) when covariates were adjusted. High animal protein intake was correlated with overexpression of RhoA in tumors with estrogen receptor-positive (ER+: β = 0.230, p < 0.05), ALNM+ (β = 0.238, p < 0.05), and vascular invasion (VI+: β = 0.313, p < 0.01). Animal protein intake was correlated with the overexpression of VEGFR2 when tumors were positive for hormonal receptors (ER+: β = 0.299, p < 0.01; PR+: β = 0.296, p < 0.01). Based on the PCA outputs, protein provided by whole meat (white and red meat) was associated inversely with RhoA expression in ALNM+ (β = − 0.253, p < 0.05) and premenopausal women (β = − 0.285, p < 0.01) in adjusted models. Whole meat was correlated with VEGFR2 overexpression in VI+ (β = 0.288, p < 0.05) and premenopausal status (β = 0.300, p < 0.05) in adjusted models. A group composed of dairy products and legumes was correlated with the overexpression of RhoA (β = 0.249, p < 0.05) and VEGF-A (β = 0.297, p < 0.05) in VI+.ConclusionsBased on the multivariate findings, the dietary protein could associate with the overexpression of RhoA and VEGF-VEGFR2 in favor of lymphatic and vascular metastasis in BC patients.
Highlights
Breast cancer (BC) is the most frequently diagnosed malignancy in females in many countries [1]
Despite the previous findings suggested an association between protein intake and increased risk of metastasis [9, 10], a few experimental studies showed the effects of high protein content in association with augmented molecular alterations in promoting metastasis [11]
Logistic regression analysis showed that the second quartile of “whole meat” pattern appeared to associate inversely with fold changes in the expression of studied genes (ORRhoA = 0.24, 95% CI 0.07–0.83; ORVEGF-A = 0.26, 95% CI 0.07–0.97; ORVEGFR2 = 0.27, 95% CI 0.08–0.96)
Summary
Breast cancer (BC) is the most frequently diagnosed malignancy in females in many countries [1]. Sufficient epidemiologic evidence has revealed the association between some lifestyle-related risk factors and the BC risk [4]. It is far less understood how dietary factors can take part in cancer progression toward the formation of metastasis [5]. In a meta-analysis of prospective studies, it has been documented that higher protein intake from red and processed meat is a potential risk factor for BC [6]. We aimed to study the association between dietary intake of protein and tumoral expression levels of Ras homologous gene family member A (RhoA), vascular endothelial growth factor-A (VEGF-A), and VEGF receptor-2 (VEGFR2) in primary breast cancer (BC) patients
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