Table 2.

Ethnic, individual and environmental factors modifying the susceptibility to milk’s nutrigenomic effects

Genetic and environmental predisposition factors of milk consumers	Nutrigenomic effects in milk consumers enhancing breast carcinogenesis
Lactase (LCT) persistence	Tolerance to higher quantities of cow’s milk intake compared to individuals with lactase non-persistence (Asian populations)
IGF1 single nucleotide polymorphisms with enhanced IGF-1 expression	Genetically predisposed IGF-1 hyper-responders may be at increased risk for milk-induced IGF-1 signal transduction
Variations in the prevalence of BRCA1 loss-of-function mutations	Enhanced IGF-1 signaling compared to ethnic groups with lower prevalence of BRCA1 mutations
Variations in the frequency of adipogenic FTO gene polymorphism	Synergism of milk-derived estrogen exposure and FTO-mediated estrogen signaling
Molecular heterogeneity of hormone receptor expression (ER+, ER−, PR+, PR−, HER2+, HER2−, triple negative BCa)	Milk signaling may preferentially promote ER-positive BCa
Variations in cow’s milk exposure during vulnerable periods of breast development, mammary branching morphogenesis, and tubular end bud formation	Enhanced risk of breast carcinogenesis by lifetime milk exposure including pregnancy (fetal overgrowth, increased birthweight), childhood and puberty (early menarche, increased longitudinal bone length), and pre- and postmenopausal periods
Variations in the dietary intake of high glycemic carbohydrates in combination with milk (milk + sugar); variations in the prevalence of type 2 diabetes	Western populations exposed to high glycemic load diets exhibit increased serum insulin and IGF-1 levels; diabetes type 2 is associated with increased risk of BCa
Quantitative and qualitative variations in protein intake	High milk protein (yogurt, cheese) and animal protein (meat) intake further increase serum IGF-1 concentrations
Variations in frequency and duration of artificial estrogen administration	Synergism of milk-induced and iatrogenic estrogen exposure enhancing estrogen and IGF-1 signaling
Variations in breastfeeding versus artificial formula feeding	Artificial formula feeding during the postnatal period may deviate postnatal breast morphogenesis via increased FTO expression
Variations in the mode and duration of breastfeeding	Reduced risk of BCa by prolonged breastfeeding of the offspring
Maternal variations in the duration of breastfeeding	Reduced risk of BCa in mothers who offer prolonged breastfeeding to their infants