Plasma Levels of Acid-labile Subunit, Free Insulin-like Growth Factor-I, and Prostate Cancer Risk: a Prospective Study

Overview

Journal Cancer Epidemiol Biomarkers Prev

Specialties Biochemistry
Oncology
Public Health

Date 2010 Feb 10

PMID 20142246

Citations 10

Authors

Lorelei A Mucci

Jennifer R Stark

Michael N Pollak

Haojie Li

Tobias Kurth

Meir J Stampfer

Jing Ma

Affiliations

Soon will be listed here.

Abstract

Background: The acid-labile subunit (ALS) acts in the insulin-like growth (IGF) system by binding circulating IGF-I in a ternary complex with binding protein (IGFBP)-3 to prevent IGF-I from crossing the endothelial barrier. Given the role of the IGF system in prostate cancer, ALS may influence carcinogenesis by modulating IGF-I levels or bioavailability.

Methods: We undertook a prospective study nested in the Physicians' Health Study to examine ALS, free IGF-I, and prostate cancer. We assayed circulating levels of ALS and IGF components among 545 incident cases and 545 matched controls. We calculated relative risks (RR) and 95% confidence intervals (95% CI) adjusted for life-style factors, total IGF-I, and IGFBP3.

Results: ALS was positively correlated with total IGF-I (r = 0.58), IGFBP3 (r = 0.68), and free IGF-I (r = 0.36). Comparing highest versus lowest quartiles, we found no association between free IGF-I and prostate cancer risk (RR, 0.9; 95% CI, 0.6-1.3). In contrast, ALS was positively associated with risk among men in the 2nd (RR, 1.5; 94% CI, 1.0-2.3), 3rd (RR, 1.6; 94% CI, 1.1-2.5), and 4th quartiles (RR, 1.4; 94% CI, 0.9-2.1) compared with lowest quartile. The association was stronger for advanced stage tumors (RR, 2.0; 94% CI, 0.8-4.6). There was a suggestion of an interaction between ALS and total IGF-I, whereby high circulating IGF-I was associated with an increased risk of advanced prostate cancer among men with low but not higher ALS levels.

Discussion: Plasma ALS is positively associated with prostate cancer risk, and may interact biologically with IGF-I to affect carcinogenesis. These data provide further support for the role of the IGF axis in prostate cancer.

Citing Articles

Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition.

Cheng T, Noor U, Watts E, Pollak M, Wang Y, McKay J BMC Cancer. 2024; 24(1):676.

PMID: 38831273 PMC: 11145848. DOI: 10.1186/s12885-023-11425-w.

Circulating Insulin-Like Growth Factor 1-Related Biomarkers and Risk of Lethal Prostate Cancer.

Ma C, Wang Y, Wilson K, Mucci L, Stampfer M, Pollak M JNCI Cancer Spectr. 2022; 6(1).

PMID: 35047751 PMC: 8763370. DOI: 10.1093/jncics/pkab091.

Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis.

Harrison S, Lennon R, Holly J, Higgins J, Gardner M, Perks C Cancer Causes Control. 2017; 28(6):497-528.

PMID: 28361446 PMC: 5400803. DOI: 10.1007/s10552-017-0883-1.

Growth hormone replacement therapy reduces risk of cancer in adult with growth hormone deficiency: A meta-analysis.

Li Z, Zhou Q, Li Y, Fu J, Huang X, Shen L Oncotarget. 2016; 7(49):81862-81869.

PMID: 27835910 PMC: 5348436. DOI: 10.18632/oncotarget.13251.

Correlation of Circulating Acid-Labile Subunit Levels with Insulin Sensitivity and Serum LDL Cholesterol in Patients with Type 2 Diabetes: Findings from a Prospective Study with Rosiglitazone.

Lai Y, Li H, Wu T, Jeng C, Chuang L PPAR Res. 2014; 2014:917823.

PMID: 24966876 PMC: 4055636. DOI: 10.1155/2014/917823.

References

Li H, Ji C, Wang W, Hu Y . A twin study for serum leptin, soluble leptin receptor, and free insulin-like growth factor-I in pubertal females. J Clin Endocrinol Metab. 2005; 90(6):3659-64. DOI: 10.1210/jc.2004-2079. View

Lacey Jr J, Hsing A, Fillmore C, Hoffman S, Helzlsouer K, Comstock G . Null association between insulin-like growth factors, insulin-like growth factor-binding proteins, and prostate cancer in a prospective study. Cancer Epidemiol Biomarkers Prev. 2001; 10(10):1101-2. View

Ueki I, Ooi G, Tremblay M, Hurst K, Bach L, Boisclair Y . Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system. Proc Natl Acad Sci U S A. 2000; 97(12):6868-73. PMC: 18767. DOI: 10.1073/pnas.120172697. View

Chan J, Stampfer M, Giovannucci E, Gann P, Ma J, Wilkinson P . Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science. 1998; 279(5350):563-6. DOI: 10.1126/science.279.5350.563. View

Stattin P, Rinaldi S, Biessy C, Stenman U, Hallmans G, Kaaks R . High levels of circulating insulin-like growth factor-I increase prostate cancer risk: a prospective study in a population-based nonscreened cohort. J Clin Oncol. 2004; 22(15):3104-12. DOI: 10.1200/JCO.2004.10.105. View

Allen N, Key T, Appleby P, Travis R, Roddam A, Rinaldi S . Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol Biomarkers Prev. 2007; 16(6):1121-7. DOI: 10.1158/1055-9965.EPI-06-1062. View

Kostecka Y, Blahovec J . Insulin-like growth factor binding proteins and their functions (minireview). Endocr Regul. 1999; 33(2):90-4. View

Roddam A, Allen N, Appleby P, Key T, Ferrucci L, Carter H . Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies. Ann Intern Med. 2008; 149(7):461-71, W83-8. PMC: 2584869. DOI: 10.7326/0003-4819-149-7-200810070-00006. View

Furstenberger G, Senn H . Insulin-like growth factors and cancer. Lancet Oncol. 2002; 3(5):298-302. DOI: 10.1016/s1470-2045(02)00731-3. View

10.

Silha J, Gui Y, Modric T, Suwanichkul A, Durham S, Powell D . Overexpression of the acid-labile subunit of the IGF ternary complex in transgenic mice. Endocrinology. 2001; 142(10):4305-13. DOI: 10.1210/endo.142.10.8427. View

11.

Johansson J, Andren O, Andersson S, Dickman P, Holmberg L, Magnuson A . Natural history of early, localized prostate cancer. JAMA. 2004; 291(22):2713-9. DOI: 10.1001/jama.291.22.2713. View

12.

Yu H, Rohan T . Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst. 2000; 92(18):1472-89. DOI: 10.1093/jnci/92.18.1472. View

13.

Harman S, Metter E, Blackman M, Landis P, Carter H . Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostate cancer. J Clin Endocrinol Metab. 2000; 85(11):4258-65. DOI: 10.1210/jcem.85.11.6990. View

14.

Holly J, Gunnell D, Davey Smith G . Growth hormone, IGF-I and cancer. Less intervention to avoid cancer? More intervention to prevent cancer?. J Endocrinol. 1999; 162(3):321-30. DOI: 10.1677/joe.0.1620321. View

15.

Firth S, Baxter R . Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002; 23(6):824-54. DOI: 10.1210/er.2001-0033. View

16.

Chan J, Stampfer M, Ma J, Gann P, Gaziano J, Pollak M . Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer. J Natl Cancer Inst. 2002; 94(14):1099-106. DOI: 10.1093/jnci/94.14.1099. View

17.

BAXTER R . Insulin-like growth factor binding proteins in the human circulation: a review. Horm Res. 1994; 42(4-5):140-4. DOI: 10.1159/000184186. View

18.

Juul A, Andersson A, Pedersen S, Jorgensen J, Christiansen J, Groome N . Effects of growth hormone replacement therapy on IGF-related parameters and on the pituitary-gonadal axis in GH-deficient males. A double-blind, placebo-controlled crossover study. Horm Res. 1998; 49(6):269-78. DOI: 10.1159/000023186. View

19.

Woodson K, Tangrea J, Pollak M, Copeland T, Taylor P, Virtamo J . Serum insulin-like growth factor I: tumor marker or etiologic factor? A prospective study of prostate cancer among Finnish men. Cancer Res. 2003; 63(14):3991-4. View

20.

BAXTER R . Circulating levels and molecular distribution of the acid-labile (alpha) subunit of the high molecular weight insulin-like growth factor-binding protein complex. J Clin Endocrinol Metab. 1990; 70(5):1347-53. DOI: 10.1210/jcem-70-5-1347. View