Interaction of insulin-like growth factor-I and insulin resistance - related genetic variants with lifestyle factors on postmenopausal breast cancer risk

摘要: Genetic variants and traits in metabolic signaling pathways may interact with obesity, physical activity, exogenous estrogen (E), influencing postmenopausal breast cancer risk, but these inter-related are incompletely understood. We used 75 single-nucleotide polymorphisms (SNPs) genes related to insulin-like growth factor-I (IGF-I)/insulin resistance (IR) pathways, data from 1003 women Women’s Health Initiative Observation ancillary studies. Stratifying via obesity lifestyle modifiers, we assessed the role of IGF-I/IR (fasting IGF-I, IGF-binding protein 3, insulin, glucose, homeostatic model assessment-insulin resistance) risk as a mediator or factor. Seven SNPs IGF-I INS were associated risk. These associations differed between non-obese/active obese/inactive E non-users users. The mediation effects on relationship strata, only roughly 35% due was mediated by traits. Similarly, carriers 20 PIK3R1, AKT1/2, MAPK1 (signaling pathways–genetic variants) had different proportion SNP–cancer explained varied 45–50% strata. Our findings suggest that genetic factors, altering partially through other than Unraveling gene–phenotype–lifestyle interactions will provide potential targets clinical trials for prevention intervention strategies reduce