| Abstract
| - Background Excessive energy intake tends to increase circulating levels of insulin and free insulin-like growth factor-1 (IGF-I), which may increase risk of some cancers that are common in Western countries. However, the relative importance of these hormonal factors during pre-adulthood and adulthood is unknown. Methods We prospectively examined height, as a marker of pre-adult IGF-I bioactivity, and modifiable adult determinants of insulin secretion, in relation to risk of cancer, particularly Western-related cancers (colon, pancreas, kidney, and aggressive prostate cancers) in 47 690 male health professionals. Information about dietary and lifestyle factors for these men was collected at baseline (1986) and was updated periodically. A C-peptide score, representing insulin secretion, was created by using body mass, physical activity, and diet in a stepwise linear regression to predict C-peptide level, in a sample of 263 cohort members. Results From 1986 to 1998, we documented 3270 incident cancers (excluding the less aggressive prostate cancers). Greater body mass index, lower physical activity, and a Western dietary pattern were independent predictors of higher plasma C-peptide levels in the sample. A C-peptide score, based on these variables, was positively related to risk of Western-related cancers, but not to other cancer types in the entire cohort. Height was also only related to Western-related cancers. For Western-related cancers, 29% (95% CI: 16%, 48%) were attributed to C-peptide scores above the first decile, 30% (95% CI: 11%, 58%) to heights ≥66 inches, and 49% (95% CI: 30%, 69%) to both factors combined. For total cancers, 29% (95% CI: 16%, 46%) were attributable to both factors. Conclusions Maximal growth in the pre-adult period and hyperinsulinaemia during adulthood may largely underlie the excess risk of some cancers that are common in Western populations. A substantial proportion of these cancers may be modifiable in adulthood, through alterations in body weight, sedentary behaviour, and dietary patterns that stimulate hyperinsulinaemia.
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