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

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Abstract

Purpose

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.

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Acknowledgments

The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study II (CPS-II) cohort. The authors thank the CPS-II participants and Study Management Group for their invaluable contributions to this research. The authors would also like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. This study was supported by the American Cancer Society and the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services.

Conflict of interest

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Authors and Affiliations

  1. Epidemiology Research Program, American Cancer Society, National Home Office, 250 Williams Street, Atlanta, GA, 30303-1002, USA

    Eric J. Jacobs & Christina C. Newton

  2. Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Debra T. Silverman, Leticia M. Nogueira, Demetrius Albanes & Rachael Z. Stolzenberg-Solomon

  3. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

    Satu Männistö

  4. Department of Oncology, McGill University, Montreal, Canada

    Michael Pollak

Authors
  1. Eric J. Jacobs
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  2. Christina C. Newton
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  3. Debra T. Silverman
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Correspondence to Eric J. Jacobs.

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Jacobs, E.J., Newton, C.C., Silverman, D.T. et al. Serum transforming growth factor-β1 and risk of pancreatic cancer in three prospective cohort studies. Cancer Causes Control 25, 1083–1091 (2014). https://doi.org/10.1007/s10552-014-0409-z

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  • DOI: https://doi.org/10.1007/s10552-014-0409-z

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