Serum Insulin‐like Growth Factors, Insulin‐like Growth Factor‐binding Protein‐3, and Risk of Lung Cancer Death: A Case‐control Study Nested in the Japan Collaborative Cohort (JACC) Study

To elucidate the roles of insulin‐like growth factors (IGFs) in the development of lung cancer, we conducted a case‐control study nested within the Japan Collaborative Cohort Study. Serum samples were collected at baseline from 39 140 men and women between 1988 and 1990. We measured serum IGF‐I, IGF‐II, and IGF‐binding protein‐3 (IGFBP‐3) in 194 case subjects who subsequently died from lung cancer during an 8‐year follow‐up and in 9351 controls. The odds ratios (ORs), adjusted for smoking and other covariates, were smaller with higher levels of IGF‐II and IGFBP‐3. The ORs across quartiles were 0.41 (95% confidence interval [CI], 0.27–0.63), 0.47 (0.31–0.71), and 0.67 (0.46–0.98) for IGF‐II (trend P=0.018), and 0.55 (95% CI, 0.37–0.81), 0.54 (0.36–0.82), and 0.67 (0.45–1.01) for IGFBP‐3 (trend P=0.037). These peptides were not independently related to lung cancer risk when mutually adjusted. The risk was increased in the highest vs. the lowest quartile of IGF‐I only after controlling for IGFBP‐3 (OR, 1.74; 95% CI, 1.08–2.81). Limiting subjects to those followed for ≥3 years strengthened the negative associations of IGF‐II and IGFBP‐3, whereas the ORs for IGF‐I generally decreased. A higher level of circulating IGFBP‐3 and/or IGF‐II may decrease lung cancer risk. Elevated serum IGF‐I may increase the risk, but this could partly be attributable to latent tumors.