A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk.
Travis RC., Appleby PN., Martin RM., Holly JMP., Albanes D., Black A., Bueno-de-Mesquita HBA., Chan JM., Chen C., Chirlaque M-D., Cook MB., Deschasaux M., Donovan JL., Ferrucci L., Galan P., Giles GG., Giovannucci EL., Gunter MJ., Habel LA., Hamdy FC., Helzlsouer KJ., Hercberg S., Hoover RN., Janssen JAMJL., Kaaks R., Kubo T., Le Marchand L., Metter EJ., Mikami K., Morris JK., Neal DE., Neuhouser ML., Ozasa K., Palli D., Platz EA., Pollak M., Price AJ., Roobol MJ., Schaefer C., Schenk JM., Severi G., Stampfer MJ., Stattin P., Tamakoshi A., Tangen CM., Touvier M., Wald NJ., Weiss NS., Ziegler RG., Key TJ., Allen NE.
The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.