title: Vasoactive peptides with angiogenesis-regulating activity predict cancer risk in males.
abstract: BACKGROUND
  Tumor development requires angiogenesis, and antiangiogenesis has been introduced in the treatment of cancer patients; however, how the cardiovascular phenotype correlates with cancer risk remains ill-defined. Here, we hypothesized that vasoactive peptides previously implicated in angiogenesis regulation predict long-term cancer risk.
  
  
  METHODS
  We measured midregional proatrial natriuretic peptide (MR-proANP), proadrenomedullin (MR-proADM), and C-terminal preprovasopressin (copeptin) in fasting plasma from participants of the Malmö Diet and Cancer Study that were free from cancer prior to the baseline exam in 1991 to 1994 (1,768 males and 2,293 females). We used Cox proportional hazards models to determine the time to first cancer event in relation to baseline levels of vasoactive peptides during a median follow-up of 15 years.
  
  
  RESULTS
  First cancer events occurred in 366 males and in 368 females. In males, one SD increase of MR-proANP, copeptin, and MR-proADM was independently related to incident cancer [HR (95% CI)] by 0.85 (0.74-0.96), P = 0.012; 1.17 (1.04-1.32), P = 0.009; and 1.12 (0.99-1.26), P = 0.065, respectively, and a summed biomarker score identified an almost 2-fold difference in cancer risk between the top and bottom quartile (P < 0.001). In younger males, the biomarker score identified a more than 3-fold increase in risk between the top and bottom quartile (P < 0.001). Among females, we found no relationship between biomarkers and cancer incidence.
  
  
  CONCLUSIONS
  Our data suggest that vasoactive peptide biomarkers predict cancer risk in males, particularly in younger males.
  
  
  CONCLUSIONS
  Our findings may have implications for cancer risk prediction and present novel, potentially drug modifiable, mechanisms underlying cancer development.
authors.affiliation: Department of Clinical Sciences, Lund University, Section of Oncology, Lund, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Belting
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012307:Risk Factors; D015996:Survival Rate; D013548:Sweden / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D006020:Glycopeptides; D010446:Peptide Fragments; D011498:Protein Precursors; C048197:copeptins; C088633:proadrenomedullin; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor