Artificial neural network-based exploration of gene-nutrient interactions in folate and xenobiotic metabolic pathways that modulate susceptibility to breast cancer

• Increased exposure to estrogen and low folate intake increase breast cancer risk.
• The prediction accuracy of the current ANN model was 94.2% for the breast cancer.
• Increased intake of folate (400 μg/day) decreases breast cancer risk by 33.33%.
• ER and PR expression was shown to restore in the presence of adequate folate.
• Folate decreases methylation of BRCA1 and EC-SOD.

In the current study, an artificial neural network (ANN)-based breast cancer prediction model was developed from the data of folate and xenobiotic pathway genetic polymorphisms along with the nutritional and demographic variables to investigate how micronutrients modulate susceptibility to breast cancer. The developed ANN model explained 94.2% variability in breast cancer prediction. Fixed effect models of folate (400 μg/day) and B12 (6 μg/day) showed 33.3% and 11.3% risk reduction, respectively. Multifactor dimensionality reduction analysis showed the following interactions in responders to folate: RFC1 G80A × MTHFR C677T (primary), COMT H108L × CYP1A1 m2 (secondary), MTR A2756G (tertiary). The interactions among responders to B12 were RFC1G80A × cSHMT C1420T and CYP1A1 m2 × CYP1A1 m4. ANN simulations revealed that increased folate might restore ER and PR expression and reduce the promoter CpG island methylation of extra cellular superoxide dismutase and BRCA1. Dietary intake of folate appears to confer protection against breast cancer through its modulating effects on ER and PR expression and methylation of EC-SOD and BRCA1.