title: Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer.
abstract: 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; P(trend) = .02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; P(trend) = .02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (P(trend) = .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.
  
  
  CONCLUSIONS
  Elevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.
authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Rm 3044, Bethesda, MD 20892-7242, USA. daa@nih.gov
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Wright
authors.forename: Satu
authors.initials: S
authors.lastname: Männistö
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.forename: Kirk
authors.initials: K
authors.lastname: Snyder
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
mesh_terms: D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015992:Body Mass Index; D016022:Case-Control Studies; D005215:Fasting; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007120:Immunochemistry; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D016015:Logistic Models; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D007328:Insulin; D013002:Somatomedins
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