Linking Physical Activity to Breast Cancer Risk via the Insulin/Insulin-like Growth Factor Signaling System, Part 2: The Effect of Insulin/Insulin-like Growth Factor Signaling on Breast Cancer Risk.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational (prospective cohort and Mendelian randomization) studies
PubMed 36464995 · doi:10.1158/1055-9965.EPI-22-0505
What was done
The authors conducted a systematic review and meta-analysis of 19 prospective cohort studies and 4 Mendelian randomization studies examining the relationship between markers of the insulin/insulin-like growth factor (IGF) signaling system (including IGFs, IGF binding proteins [IGFBPs], and insulin resistance markers) and breast cancer risk. Risk of bias was evaluated and overall evidence quality was rated using the GRADE framework.
What was found
Meta-analysis of prospective cohort studies found that higher IGF-1 levels increased the risk of breast cancer, a result corroborated by Mendelian randomization studies. IGFBP-3 was not associated with breast cancer risk. Fasting insulin and connecting-peptide (C-peptide) meta-analyses showed small risk increases, but confidence intervals were wide and crossed the null. Exact numerical effect sizes, point estimates, and confidence intervals were not reported in the abstract. There were insufficient studies to evaluate other insulin/IGF signaling markers.
Why it matters
These findings suggest that while IGF-1 is associated with breast cancer risk, the broader insulin/IGF signaling axis does not provide strong biological plausibility as the mediating pathway through which physical activity reduces breast cancer risk.
Limits
The abstract reports no numerical effect estimates or confidence intervals. The overall body of literature was rated between very low and moderate quality, limited by a scarcity of high-quality studies, wide confidence intervals crossing the null, and insufficient data on additional pathway biomarkers.
Cited by
- supports Exercise reduces levels of insulin and insulin-like growth factor (IGF), which promote cancer cell growth and division.