Hyperinsulinemia predicts fetal liver cancer but is inversely associated with fatal cancer at some other sites - The Paris Prospective Study

OBJECTIVE - To investigate whether insulin is a risk factor for death by si te-specific cancers. RESEARCH DESIGN AND METHODS - This was a prospective cohort study of 6,237 nondiabetic French working men between ages 44 and 55 years at baseline fro m the Paris Prospective Study cohort. Death by site-specific cancers was in vestigated in relation to baseline insulin concentrations during lasting an d 2 h after a 75-g oral glucose tolerance test. RESULTS - Of the original 6,237 men in the cohort, 1,739 died over the 23.8 years of follow-up, 778 (45%) from cancer. Baseline hyperinsulinemia. both fasting and 2-h, was significantly associated with fatal liver cancer, wit h age-adjusted standardized hazards ratios of 2.72 (95% CI 1.87-3.94) and 3 .41 (2.23-5.21). in contrast, lasting hyperinsulinemia was inversely associ ated with fatal lip, ornl cavity, and pharynx cancer and larynx cancer, wit h hazards ratios of 0.55 (0.41-0.75) and 0.63 (0.47-0.83), respectively; 2- h insulin concentrations were inversely associated with stomach and larynx cancers (hazards ratios 0.62 [0.43-0.90] and 0.66 [0.50-0.89], respectively ). These relationships were stable after adjusting for other risk factors. Insulin concentrations remained negatively associated with deaths from thes e cancers in analyses restricted to men who smoked and in those who were no t chronic alcohol consumers. CONCLUSIONS - Peripheral hyperinsulinemia, indicative of very high portal i nsulin concentrations, predicted fatal liver cancer in these nondiabetic me n, but was inversely associated with fatal lip, oral cavity, and pharynx ca ncer; stomach cancer: and larynx cancer.