Hyperinsulinemia Predicts Fatal Liver Cancer but Is Inversely Associated With Fatal Cancer at Some Other Sites

Abstract

OBJECTIVE—To investigate whether insulin is a risk factor for death by site-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 from the Paris Prospective Study cohort. Death by site-specific cancers was investigated in relation to baseline insulin concentrations during fasting and 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, with age-adjusted standardized hazards ratios of 2.72 (95% CI 1.87–3.94) and 3.41 (2.23–5.21). In contrast, fasting hyperinsulinemia was inversely associated with fatal lip, oral cavity, and pharynx cancer and larynx cancer, with 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 these cancers in analyses restricted to men who smoked and in those who were not chronic alcohol consumers.

CONCLUSIONS—Peripheral hyperinsulinemia, indicative of very high portal insulin concentrations, predicted fatal liver cancer in these nondiabetic men, but was inversely associated with fatal lip, oral cavity, and pharynx cancer; stomach cancer; and larynx cancer.