Journal of the National Cancer Institute Advance Access originally published online on August 21, 2009
JNCI Journal of the National Cancer Institute 2009 101(18):1272-1279; doi:10.1093/jnci/djp260
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Published by Oxford University Press 2009.
ARTICLES |
Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Prostate Cancer
Affiliations of authors: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (DA, SJW); Department of Pathology, University of Illinois at Chicago College of Medicine, Chicago, IL (MEW); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (SM, JV); Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN (PJL); Information Management Services, Inc, Silver Spring, MD (KS)
Correspondence to: Demetrius Albanes, MD, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Rm 3044, Bethesda, MD 20892-7242 (e-mail: daa{at}nih.gov).
Background: The mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear.
Methods: We investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case–cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5–12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided.
Results: Insulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8% higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10% and 6% higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95% confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95% CI = 0.86 to 3.56; and OR = 2.55, 95% CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; Ptrend = .02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; Ptrend = .02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (Ptrend = .38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100 000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100 000 person-years in the highest quartile.
Conclusion: Elevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.
| CONTEXT AND CAVEATS Prior knowledge Insulin-like growth factors have several effects, including mitogenic and growth-stimulatory effects, that may be involved in prostate carcinogenesis; however, the association of circulating insulin levels with prostate cancer risk is unclear. Study design A case–cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. Insulin and glucose concentrations were determined in fasting serum samples that were collected 5–12 years before diagnosis of prostate cancer. Contribution There may be an increasing risk of prostate cancer across the normal range of insulin concentrations, although no association was observed between overall risk of prostate cancer and serum glucose levels. Implications Additional investigations on the association between insulin level and risk of prostate cancer are warranted, especially in nonsmoking populations and other races and ethnicities. Limitations The number of case subjects with prostate cancer in this study was small. Subjects included only Finnish male smokers (all whites), and so the findings may not be generalizable to other populations. From the Editors
|
Manuscript received December 18, 2008; revised June 22, 2009; accepted July 14, 2009.
Related Article in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2009 101: 1221.
This article has been cited by other articles:
|
|
 |
|
  E. J. Jacobs and S. M. Gapstur Cholesterol and Cancer: Answers and New Questions Cancer Epidemiol. Biomarkers Prev., November 1, 2009; 18(11): 2805 - 2806. [Full Text] [PDF]
|
|