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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 39140 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.

Background: Perceived mental stress has been associated with risk of coronary heart disease (CHD) in white men, but no prospective data are available for other ethnic groups., Methods and Results: From 1988 to 1990, a total of 73 424 Japanese (30 180 men and 43 244 women), aged 40 to 79 years, without a history of stroke, CHD, or cancer completed a lifestyle questionnaire including perception of mental stress under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study). Systematic surveillance was completed until the end of 1997, with a 580 378 person-year follow-up, and the underlying causes of death were determined according to the International Classification of Diseases, 10th revision. For women, there were 316 with total stroke, 113 with CHD, and 643 with total cardiovascular disease (CVD); for men, there were 341, 168, and 778, respectively. Women who reported high stress had a 2-fold higher age-adjusted risk of mortality from total stroke and CHD and 1.5-fold higher risk of total CVD compared with those who reported low stress. Further adjustment for known cardiovascular risk factors and selected psychological variables did not alter the associations materially. The multivariate relative risk for women who perceived high stress versus low stress was 2.24 (95% CI 1.52 to 3.31, P<0.001) for total stroke, 2.28 (95% CI 1.17 to 4.43, P=0.02) for CHD, and 1.64 (95% CI 1.25 to 2.16, P<0.001) for total CVD. For men, these relations were generally weaker but suggestive of myocardial infarction., Conclusions: Perceived mental stress was associated with increased mortality from stroke for women and with CHD for men and women.