Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

Risk Factors for Early-Onset and Very-Early-Onset Pancreatic Adenocarcinoma: A Pancreatic Cancer Case-Control Consortium (PanC4) Analysis

McWilliams, Robert R. MD*; Maisonneuve, Patrick Dip. Eng; Bamlet, William R. MS; Petersen, Gloria M. PhD§; Li, Donghui PhD; Risch, Harvey A. PhD; Yu, Herbert MD, MSc, PhD#; Fontham, Elizabeth T. H. MPH, DrPH**; Luckett, Brian PhD††; Bosetti, Cristina ScD‡‡; Negri, Eva ScD‡‡; La Vecchia, Carlo MD‡‡§§; Talamini, Renato ScD∥∥; de Mesquita, H. Bas Bueno MD, PhD¶¶; Bracci, Paige PhD##; Gallinger, Steven MD***; Neale, Rachel E. PhD†††; Lowenfels, Albert B. MD‡‡‡

doi: 10.1097/MPA.0000000000000392
Original Articles

Objectives While pancreatic cancer (PC) most often affects older adults, to date, there has been no comprehensive assessment of risk factors among PC patients younger than 60 years.

Methods We defined early-onset PC (EOPC) and very-early-onset PC (VEOPC) as diagnosis of PC in patients younger than 60 and 45 years, respectively. We pooled data from 8 case-control studies, including 1954 patients with EOPC and 3278 age- and sex-matched control subjects. Logistic regression analysis was performed to identify associations with EOPC and VEOPC.

Results Family history of PC, diabetes mellitus, smoking, obesity, and pancreatitis were associated with EOPC. Alcohol use equal to or greater than 26 g daily also was associated with increased risk of EOPC (odds ratio, 1.49; 95% confidence interval, 1.21–1.84), and there appeared to be a dose- and age-dependent effect of alcohol on risk. The point estimate for risk of VEOPC was an odds ratio of 2.18 (95% confidence interval, 1.17–4.09).

Conclusions The established risk factors for PC, including smoking, diabetes, family history of PC, and obesity, also apply to EOPC. Alcohol intake appeared to have an age-dependent effect; the strongest association was with VEOPC.

Supplemental digital content is available in the text.

From the *Department of Oncology, Mayo Clinic, Rochester, MN; †Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy; ‡Division of Biostatistics, Mayo Clinic; §Department of Health Sciences Research, Mayo Clinic, Rochester, MN; ∥Department of Gastrointestinal Medical Oncology, UT MD Anderson Cancer Center, Houston, TX; ¶Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT; #Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI; **Louisiana State University School of Public Health, New Orleans, LA; ††Tulane School of Public Health, New Orleans, LA; ‡‡Department of Epidemiology, IRCCS–Istituto di Ricerche Farmacologiche “Mario Negri,” and §§Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; ∥∥S.O.C. Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy; ¶¶National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; School of Public Health, Imperial College London, London, United Kingdom; ##Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA; ***Division of General Surgery, University of Toronto, Toronto, Ontario, Canada; †††Cancer and Population Studies Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia; and ‡‡‡Department of Surgery, Department of Family Medicine, New York Medical College, Valhalla, NY.

Received for publication December 2, 2014; accepted May 28, 2015.

Reprints: Robert R. McWilliams, MD, Department of Oncology, Mayo Clinic, 200 First St, Southwest, Rochester, MN 55905 (e-mail:

R.R.M. and P.M. are co–first authors.

The LSU study was supported by the Louisiana Board of Regents Millennium Trust Health Excellence Fund (Project 5: HEF, 2000–2005, Genetics Studies in the Acadian Population). The Pancreatic Cancer Family Registry at Memorial Sloan Kettering Cancer Center has been supported by the Prevention, Control, and Population Research Goldstein Award; the Society of Memorial Sloan Kettering Cancer Center; and the Geoffrey Beene Cancer Research Fund. The University of California San Francisco study work was supported in part by National Cancer Institute grants CA59706, CA108370, CA109767, CA89726, CA098889 (E. A. Holly, principal investigator) and by the Rombauer Pancreatic Cancer Research Fund. Cancer incidence data collection in the University of California San Francisco study was supported by the California Department of Public Health, the National Cancer Institute’s Surveillance, Epidemiology and End Results Program contract N01-PC-35136 awarded to the Northern California Cancer Center. The Yale Connecticut Study was supported by National Cancer Institute grant 5R01CA098870 (H.A.R., principal investigator). The cooperation of 30 Connecticut hospitals, including Stamford Hospital, in allowing patient access is gratefully acknowledged. The Connecticut study was approved by the State of Connecticut Department of Public Health Human Investigation Committee. Certain data used in the study were obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health. The Ontario Pancreas Cancer Study was supported by grants from the National Institutes of Health (R01 CA97075, as part of the PACGENE consortium and U01CA74783), the Lustgarten Foundation for Pancreatic Cancer Research, and the Ontario Cancer Research Network. The Italy and Milan studies were supported by the Italian Association for Cancer Research (AIRC grant no. 10068). The SEARCH study was supported by the Cancer Research Society; the Toronto contribution was supported by the National Cancer Institute of Canada, and The Netherlands contribution was supported by the Dutch Ministry of Public Health, Welfare and Sports (formerly Welfare, Health and Culture). The Mayo Clinic study was supported in part by National Cancer Institute grants P50CA102701 (Mayo Clinic SPORE in Pancreatic Cancer) and R01CA97075 (Pancreatic Cancer Genetic Epidemiology Consortium (PACGENE).

The authors declare no conflict of interest.

Author contributions: Writing of manuscript: R.R.M., P.M., A.B.L., G.M.P., R.E.N., H.A.R.; conception and design: R.R.M., P.M., A.B.L.; contribution of patients: G.M.P., D.L., H.A.R., E.T.H.F., B.L., C.B., E.N., C.L.V., R.T., H.B.B.d.M., P.B., S.G.

Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.