title: Serum transforming growth factor-β1 and risk of pancreatic cancer in three prospective cohort studies.
abstract: OBJECTIVE
  Clinically evident chronic pancreatitis is a strong risk factor for pancreatic cancer. A small Japanese cohort study previously reported that pre-diagnostic serum transforming growth factor-β1 (TGF-β1) concentration, a potential marker of subclinical pancreatic inflammation, was associated with higher risk of pancreatic cancer. We further explored this association in a larger prospective study.
  
  
  METHODS
  Serum TGF-β1 concentrations were measured in pre-diagnostic samples from 729 pancreatic cancer cases and 907 matched controls from a cohort of Finnish male smokers (the Alpa-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study) and two cohorts of US men and women, the Cancer Prevention Study-II and the Prostate Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Multivariable-adjusted odds ratios (ORs) were estimated using conditional logistic regression.
  
  
  RESULTS
  Overall, serum TGF-β1 concentration was not associated with a clear increase in pancreatic cancer risk (OR 1.36, 95 % confidence interval (CI) 0.98-1.88 for highest vs. lowest quintile, p trend = 0.20). However, this association differed significantly by follow-up time (p = 0.02). Serum TGF-β1 concentration was not associated with risk during the first 10 years of follow-up, but was associated with higher risk during follow-up after 10 years (OR 2.13, 95 % CI 1.23-3.68 for highest vs. lowest quintile, p trend = 0.001). During follow-up after 10 years, serum TGF-β1 was associated with higher risk only in the ATBC cohort, although most subjects were from ATBC during this time period and statistical evidence for heterogeneity across cohorts was limited (p = 0.14).
  
  
  CONCLUSIONS
  These results suggest that high serum TGF-β1 may be associated with increased risk of pancreatic cancer although a long follow-up period may be needed to observe this association.
authors.affiliation: Epidemiology Research Program, American Cancer Society, National Home Office, 250 Williams Street, Atlanta, GA, 30303-1002, USA, ejacobs@cancer.org.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jacobs
authors.forename: Christina C
authors.initials: CC
authors.lastname: Newton
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.forename: Leticia M
authors.initials: LM
authors.lastname: Nogueira
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Satu
authors.initials: S
authors.lastname: Männistö
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Rachael Z
authors.initials: RZ
authors.lastname: Stolzenberg-Solomon
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D053773:Transforming Growth Factor beta1