Associations between Dietary Intake of Fruits and Vegetables in Relation to Urinary Estrogen DNA Adduct Ratio

Abstract

Background Estrogen exposure plays a role in breast cancer (BC) development. A novel estrogen biomarker, the estrogen DNA adduct (EDA) ratio, was shown to be elevated in women at high-risk of BC and among BC cases. Modifiable factors may impact the EDA ratio, with studies demonstrating that resveratrol reduces EDA ratio in vitro. We sought to examine the hypothesis that dietary intake of fruits and vegetables is inversely associated with EDA ratio. Methods This analysis was conducted in 53 pre-menopausal, healthy women aged 40–45 years from a cross-sectional study in which participants provided first-void urine samples and 3-day food records. Urine samples were analyzed using ultraperformance liquid chromatography/tandem mass spectrometry. The EDA ratio was calculated as the estrogen-DNA adducts divided by estrogen metabolites and conjugates. A trend test was used to assess associations between tertiles of dietary intake using linear regression. Results After adjustment for age, total energy, percent adiposity, serum estradiol and estrone-sulfate, we observed inverse associations of EDA ratio with carbohydrate consumption (P=0.01) and vegetable intake (P =0.01). EDA ratio was inversely associated with 5 botanical groups (Chenopodiaceae: P=0.02; Umbelliferae: P=0.03; Compositae: P=0.01; Ericaceae: P=0.01; Musaceae: P=0.03) but not fruit intake overall. Conclusion Although these data require replication before conclusions are drawn, this report suggests an inverse association between vegetable and carbohydrate consumption and EDA ratio. Impact While more information is still needed, these findings suggest a link between dietary intake and a biomarker that is both associated with high-risk BC status and associated with modifiable factors.

Vegetarian dietary patterns and the risk of breast cancer in a low-risk population

“…These properties can potentially influence cancer progression and development through inhibition of metastasis, induction of apoptosis, anti-proliferative activity and inhibition of protein kinase activity ( 70 ) . Soya has been hypothesised to reduce BC risk by shifting oestrogen metabolites that are genotoxic towards other inactive forms ( 63 , 66 ) . Soya is also known to have anti-proliferative, pro-apoptotic, antiangiogenic, antioxidative and anti-inflammatory effects ( 13 ) .…”

“…Their analysis suggested a 4-6 % lower risk for each additional recommendation that was met. Several possibly protective mechanisms against cancer can be identified that are associated with the higher consumption of fruit, vegetables (47,(62)(63)(64)(65) and soya (13,66) and a lower BMI, characteristics typical of most vegans in this population. Higher intakes of non-essential amino acids, characteristic of vegan diets, regulate the insulin-glucagon axis (67)(68)(69) , and there are metabolic effects that include greater tissue sensitivity to insulin, and also decreased hepatic production and serum levels of insulin-like growth factor-1.…”

Red Clover Aryl Hydrocarbon Receptor (AhR) and Estrogen Receptor (ER) Agonists Enhance Genotoxic Estrogen Metabolism

“… 2 Breast cancer risk is also influenced by estrogen metabolism, and the genotoxic estrogen quinones formed in this process 3 − 5 can be modulated by dietary means, including botanical dietary supplements (BDSs). 2 , 6 , 7 As traditional hormone therapy (HT) is associated with an increased risk of breast cancer, many women use BDSs, which are perceived as safer alternatives for the relief of menopausal symptoms. 2 , 8 − 10 However, efficacy claims are not only disallowed for BDSs but also remain questionable for botanicals used in this field.…”

Leptin influences estrogen metabolism and increases DNA adduct formation in breast cancer cells

“…Although the connection between obesity and breast cancer has been well documented in various studies 10 , the molecular mechanisms fundamental for this correlation are not fully clear. Leptin, an obesity related molecule, is a key player in the progression of several types of cancer including breast cancer.…”

“…Consequently, research on compounds that affect the estrogen metabolic pathway is ongoing. Example of these compounds are the dietary supplements resveratrol and N-acetylcysteine 8 and the tumor necrosis factor-alpha (TNF-α) 9 , as well as vegetable and carbohydrate consumption 10 . …”