Objective The insulin-like growth factor (IGF) axis is thought to contribute to the growth and progression of prostate cancer. Some prospective studies support a direct association between IGF-1 and prostate cancer, in particular advanced disease, whereas both inverse and direct associations with prostate cancer have been reported for insulin-like growth factor binding protein-3 (IGFBP-3), the major IGF-1 binding protein in circulation. We prospectively investigated the associations of plasma IGF-1 and IGFBP-3 concentrations with prostate cancer detected in the PSA era.
Methods: We identified 462 prostate cancer cases diagnosed after providing a blood specimen in 1993, but before January 1998 among men in the Health Professionals Follow-up Study. Controls were 462 age-matched men without prostate cancer who had had a PSA test after providing a blood specimen. We measured plasma concentrations of IGF-1 and IGFBP-3 by ELISA. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer.
Results: Men with higher concentrations of IGF-1 (comparing extreme quartiles OR=1.37, 95% CI 0.92–2.03, p-trend=0.05) and IGFBP-3 (OR=1.62, 95% CI 1.07–2.46, p-trend=0.08) had a higher risk of prostate cancer. After mutual statistical adjustment, these associations were attenuated for both IGF-1 (OR=1.17, 95% CI 0.69–1.99, p-trend=0.29) and IGFBP-3 (OR=1.40, 95% CI 0.80–2.44, p-trend=0.56). We found no significant association of IGF-1 with regionally invasive or metastatic (≥T3b, N1, or M1) prostate cancer, although the number of these cases was small (n=42).
Conclusions: Our findings for IGF-1 and prostate cancer diagnosed in the PSA era are similar to most previous studies, albeit weaker in magnitude. Our suggestive positive findings for IGFBP-3 are similar to some studies, but in direct contrast to others.
cohort study insulin-like growth factor prostate cancer risk.
Cohen, P, Peehl, DM, Rosenfeld, RG 1994The IGF axis in the prostateHorm Metab Res268184PubMedGoogle Scholar
Cohen, P, Peehl, DM, Lamson, G, Rosenfeld, RG 1991Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial cellsJ Clin Endocri Metab73401407Google Scholar
Rajah, R, Valentinis, B, Cohen, P 1997Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-β1 on programmed cell death through a p53- and IGF-independent mechanismJ Biol Chem2721218112188CrossRefPubMedGoogle Scholar
Liu, B, Lee, HY, Weinzimer, SA, Powell, DR, Clifford, JL, Kurie, JM, et al. 2000Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-α regulate transcriptional signaling and apoptosisJ Biol Chem2753360733613CrossRefPubMedGoogle Scholar
Mantzoros, CS, Tzonou, A, Signorello, LB, Stampfer, M, Trichopoulos, D, Adami, HO 1997Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasiaBr J Cancer7611151118PubMedGoogle Scholar
Chan, JM, Stampfer, MJ, Giovannucci, E, Gann, PH, Ma, J, Wilkinson, P, et al. 1998Plasma insulin-like growth factor-I and prostate cancer risk: a prospective studyScience279563566CrossRefPubMedGoogle Scholar
Wolk, A, Mantzoros, CS, Andersson, SW, Bergström, R, Signorello, LB, Lagiou, P, et al. 1998Insulin-like growth factor I and prostate cancer risk: a population-based, case–control studyJ Natl Cancer Inst90911915CrossRefPubMedGoogle Scholar
Stattin, P, Bylund, A, Rinaldi, S, Biessy, C, Dechaud, H, Stenman, UH, et al. 2000Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective studyJ Natl Cancer Inst9219101917CrossRefPubMedGoogle Scholar
Harman, SM, Metter, EJ, Blackman, MR, Landis, PK, Carter, HB 2000Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostate cancerJ Clin Endocr Metab8542584265CrossRefPubMedGoogle Scholar
Khosravi, J, Diamandi, A, Mistry, J, Scorilas, A 2001Insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in benign prostatic hyperplasia and prostate cancerJ Clin Endocr Metab86694699CrossRefPubMedGoogle Scholar
Chokkalingam, A, Pollak, M, Fillmore, C, Gao, Y, Stanczyk, F, Deng, J, et al. 2001Insulin-like growth factors and prostate cancer: a population-based case–control study in ChinaCancer Epidemiol Biomarkers Prev10421427PubMedGoogle Scholar
Stattin, P, Rinaldi, S, Biessy, C, Stenman, UH, Hallmans, G, Kaaks, R 2004High levels of circulating insulin-like growth factor-I increase prostate cancer risk: a prospective study in a population-based nonscreened cohortJ Clin Oncol2231043112CrossRefPubMedGoogle Scholar
Chan, JM, Stampfer, MJ, Ma, J, Gann, P, Gaziano, JM, Pollak, M, et al. 2002Insulin-like growth factor-I (IGF-1) and IGF binding protein-3 as predictors of advanced-stage prostate cancerJ Natl Cancer Inst9410991109PubMedGoogle Scholar
Shi, R, Berkel, HJ, Yu, H. 2001Insulin-like growth factor-I and prostate cancer: a meta-analysisBr J Cancer85991996CrossRefPubMedGoogle Scholar
Stampfer, MJ, Willett, WC, Speizer, FE, Dysert, DC, Lipnick, R, Rosner, B, et al. 1984Test of the National Death IndexAm J Epidemiol119837839PubMedGoogle Scholar
Giovannucci, E, Rimm, EB, Liu, Y, Leitzmann, M, Wu, K, Stampfer, MJ, et al. 2003Body mass index and risk of prostate cancer in U.S. Health professionalsJ Natl Cancer Inst9512401244PubMedGoogle Scholar
Platz, EA, Leitzmann, MF, Michaud, DS, Willett, WC, Giovannucci, E 2003Interrelation of energy intake, body size, and physical activity with prostate cancer in a large prospective cohort studyCancer Res6385428548PubMedGoogle Scholar
Giovannucci, E, Pollak, M, Liu, Y, Platz, EA, Rimm, EB, Willett, WC 2003Nutritional predictors of insulin-like growth factor I and their relationships to cancer in menCancer Epidemiol Biomarkers Prev128489PubMedGoogle Scholar
1.Department of EpidemiologyJohns Hopkins Bloomberg School of Public Health; and the Brady Urological Institute and the Kimmel Comprehensive Cancer Center, Johns Hopkins Medical InstitutionsBaltimoreUSA
2.Cancer Prevention Research Unit, Departments of Medicine and OncologyJewish General Hospital and McGill UniversityMontrealCanada
3.Department of Health and Human ServicesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of HealthBethesdaUSA
4.Departments of Nutrition and Epidemiology, Department of MedicineHarvard School of Public Health, and the Channing Laboratory, Harvard Medical School and Brigham & Women’s HospitalBoston