Serum transforming growth factor-β1 and risk of pancreatic cancer in three prospective cohort studies.

Abstract

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. 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. 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 10years of follow-up, but was associated with higher risk during follow-up after 10years (OR 2.13, 95% CI 1.23-3.68 for highest vs. lowest quintile, p trend=0.001). During follow-up after 10years, 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). 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.