Genetic variants and traits related to insulin-like growth factor-I and insulin resistance and their interaction with lifestyles on postmenopausal colorectal cancer risk.

摘要: Genetic variants and traits in metabolic signaling pathways may interact with lifestyle factors such as obesity, physical activity, exogenous estrogen (E), influencing postmenopausal colorectal cancer (CRC) risk, but these interrelated are not fully understood. In this case-cohort study, we examined 33 single-nucleotide polymorphisms (SNPs) genes related to insulin-like growth factor-I (IGF-I)/ insulin resistance (IR) pathways, using data from 704 women Women's Health Initiative Observation ancillary studies. Stratifying by the modifiers, assessed effects of IGF-I/IR (fasting total free IGF-I, IGF binding protein-3, insulin, glucose, homeostatic model assessment-insulin resistance) on CRC risk a mediator or factor. Six SNPs INS, IGFBP3 were associated those associations differed between non-obese/active obese/inactive E nonusers users. Roughly 30% due SNP was mediated traits. Likewise, carriers 11 IRS1 AKT1/2 (signaling pathway-related genetic variants) had different strata, proportion SNP-cancer association explained varied 50%. Our findings suggest that E, altering through traits, also pathways. Unraveling gene-phenotype-lifestyle interactions will provide potential targets clinical trials for prevention intervention strategies reduce risk.