Plasma insulin-like growth Factor-Binding protein 7 predicts 20-Year Cancer-Specific and overall survival in ARIC

Insulin-like growth factor-binding protein 7 (IGFBP7) may influence physiology by modulating IGF signaling and/or by IGF-independent mechanisms. Prior studies suggest positive associations of circulating IGFBP7 with cancer incidence and all-cause mortality. We analyzed whether IGFBP7 is associated with cancer incidence, cancer mortality, and all-cause mortality.

We conducted a prospective cohort analysis of 10,834 participants with no cancer history for cancer analyses, and 11,761 participants for all-cause mortality analyses in the Atherosclerosis Risk in Communities study. Participants aged 46-70 years were followed for >2 decades. Plasma IGFBP7 was measured by SomaScan® 5K assay (relative fluorescence units). Incident cancers were ascertained primarily by state cancer registry linkage and mortality confirmed by death certificates. We estimated the association between quartiles of log2-transformed IGFBP7 and outcomes using Cox proportional hazards regression adjusting for age, sex, race/center, and major risk factors, and predicted 20-year survival across IGFBP7 quartiles.

IGFBP7 was positively associated with cancer mortality (1,420 cancer deaths; Q4 vs. Q1: HR = 1.27, 95% CI 1.08-1.50), especially lung (HR = 1.48, 95% CI 1.07-2.05), but not with cancer incidence (3,347 cases; HR = 1.01, 95% CI 0.91-1.12). IGFBP7 was positively associated with all-cause mortality (6,981 deaths; HR = 1.33, 95% CI 1.23-1.43). The highest IGFBP7 quartile had lowest 20-year predicted cancer-specific survival (unadjusted model only) and survival overall. IGFBP7 was not strongly correlated with IGF-1.

High circulating IGFBP7 may be a risk factor for cancer mortality, especially lung, and all-cause mortality. Our observations justify confirmatory studies and efforts to understand underlying mechanisms.