期刊
CANCER CAUSES & CONTROL
卷 21, 期 11, 页码 1829-1842出版社
SPRINGER
DOI: 10.1007/s10552-010-9610-x
关键词
Adiposity; Life course; Insulin-like growth factors
资金
- Cancer Research UK [C18281/A7062]
- NIHR [HTA 96/20/99, ISRCTN20141297]
- Department of Health
- Medical Research Council and Cancer Research UK
- ProMPT (Prostate Mechanisms of Progression and Treatment)
- Cambridge NIHR Comprehensive Biomedical Research Centre
- MRC [G0900871] Funding Source: UKRI
- Medical Research Council [G0900871] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0509-10242] Funding Source: researchfish
Adiposity is positively associated with advanced, metastatic, and fatal prostate cancer. Obesity-related variations in insulin-like growth factors (IGF-I and -II) and their binding proteins (IGFBPs) could underlie these associations. We investigated associations of adiposity throughout the life course (determined retrospectively) with serum levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in a population-based study of 1,106 healthy men. IGF-I and IGF-II showed inverted U-shaped associations with adult body mass index (BMI) (p quadratic model = 0.04 and 0.06, respectively), although differences between quartiles with the highest and lowest IGF-I levels were small (no more than 5 ng/ml). IGFBP-2 was strongly inversely related to adult BMI (-22% change per SD increase in BMI; 95% confidence interval (CI) -24% to -19%) and waist circumference (-18% change per SD increase in waist circumference; 95% CI -20% to -15%) (p < 0.001). IGFBP-3 was positively related to BMI (63.5 ng/ml increase per SD increase in BMI; 95% CI -2.69 to 129.8, p = 0.06). IGFBP-2 and IGFBP-3 were strongly related to body shape change from childhood to adulthood, with men who gained the most weight having the lowest IGFBP-2 (9% lower per category body shape change; 95% CI -11% to -7%, p < 0.001) and the highest IGFBP-3 (50 ng/ml increase per category; 95% CI 8 to 92, p = 0.02). We provide evidence that adiposity and change in body shape through the life course are related to the IGF system, with the largest effect of adiposity being to lower IGFBP-2, a possible marker of insulin resistance. The results suggest that circulating IGF-I levels may not be important mediators of the association of adiposity with aggressive prostate cancer, but the role of IGFBP-2 deserves further investigation.
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