title: Both low and high serum IGF-I levels associate with cancer mortality in older men.
abstract: BACKGROUND
  Although recent population-based studies suggest a U-shaped relationship between serum IGF-I concentration and all-cause mortality, the distribution of death causes underlying this association remains unclear. We hypothesized that high IGF-I levels associate with increased cancer mortality, whereas low IGF-I levels associate with increased cardiovascular disease (CVD) mortality.
  
  
  METHODS
  Serum IGF-I levels were measured in 2901 elderly men (mean age 75.4, range 69-81 yr) included in the prospective population-based Osteoporotic Fractures in Men Study (Sweden) study. Mortality data were obtained from central registers with no loss of follow-up. The statistical analyses included Cox proportional hazards regressions with or without a spline approach.
  
  
  RESULTS
  During the follow-up (mean 6.0 yr), 586 of the participants died (cancer deaths, n = 211; CVD deaths, n = 214). As expected, our data revealed a U-shaped association between serum IGF-I levels and all-cause mortality. Low as well as high serum IGF-I (quintile 1 or 5 vs. quintiles 2-4) associated with increased cancer mortality [hazard ratio (HR) = 1.86, 95% confidence interval (CI) = 1.34-2.58; and HR = 1.90, 95% CI = 1.37-2.65, respectively]. Only low serum IGF-I associated with increased CVD mortality (quintile 1 vs. quintiles 2-4, HR = 1.48, 95% CI = 1.08-2.04). These associations remained after adjustment for multiple covariates and exclusion of men who died during the first 2 yr of follow-up.
  
  
  CONCLUSIONS
  Our findings demonstrate that both low and high serum IGF-I levels are risk markers for increased cancer mortality in older men. Moreover, low IGF-I levels associate with increased CVD mortality.
authors.affiliation: Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden. johan.svensson@medic.gu.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Svensson
authors.forename: Daniel
authors.initials: D
authors.lastname: Carlzon
authors.forename: Max
authors.initials: M
authors.lastname: Petzold
authors.forename: Magnus K
authors.initials: MK
authors.lastname: Karlsson
authors.forename: Östen
authors.initials: Ö
authors.lastname: Ljunggren
authors.forename: Asa
authors.initials: A
authors.lastname: Tivesten
authors.forename: Dan
authors.initials: D
authors.lastname: Mellström
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality; D002423:Cause of Death; D015331:Cohort Studies; D005500:Follow-Up Studies; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000097:blood* / Q000378:metabolism / Q000401:mortality*; D016019:Survival Analysis; D013548:Sweden / Q000453:epidemiology
chemical_list: D007334:Insulin-Like Growth Factor I