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Family history of cancer, Ashkenazi Jewish ancestry, and pancreatic cancer risk



Individuals with a family history of cancer may be at increased risk of pancreatic cancer. Ashkenazi Jewish (AJ) individuals carry increased risk for pancreatic cancer and other cancer types.


We examined the association between family history of cancer, AJ heritage, and incident pancreatic cancer in 49 410 male participants of the prospective Health Professionals Follow-up Study. Hazard ratios (HRs) were estimated using multivariable-adjusted Cox proportional hazards models.


During 1.1 million person-years (1986–2016), 452 participants developed pancreatic cancer. Increased risk of pancreatic cancer was observed in individuals with a family history of pancreatic (HR, 2.79; 95% confidence interval [CI], 1.28–6.07) or breast cancer (HR, 1.40; 95% CI, 1.01–1.94). There was a trend towards higher risk of pancreatic cancer in relation to a family history of colorectal cancer (HR, 1.21; 95% CI, 0.95–1.55) or AJ heritage (HR, 1.29; 95% CI, 0.94–1.77). The risk was highly elevated among AJ men with a family history of breast or colorectal cancer (HR, 2.61 [95% CI, 1.41–4.82] and 1.92 [95% CI, 1.05–3.49], respectively).


Family history of pancreatic cancer was associated with increased risk of this malignancy. Family history of breast or colorectal cancer was associated with the increased risk among AJ men.

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We would like to thank the participants and staff of the HPFS for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. We assume full responsibility for analyses and interpretation of the data. The HPFS is supported by U.S. National Institutes of Health (NIH) grants (UM1 CA167552 and U01 CA167552). This work was additionally supported by NIH R01 CA205406 and the Broman Fund for Pancreatic Cancer Research to K.N.; by NIH R01 CA124908 and P50 CA127003, the Robert T. and Judith B. Hale Fund for Pancreatic Cancer, Perry S. Levy Fund for Gastrointestinal Cancer Research, and Pappas Family Research Fund for Pancreatic Cancer to C.S.F.; by NIH R35 CA197735 to S.O.; and by Hale Center for Pancreatic Cancer Research, NIH/National Cancer Institute (NCI) U01 CA210171, Department of Defense CA130288, Lustgarten Foundation, Stand Up to Cancer, Pancreatic Cancer Action Network, Noble Effort Fund, Wexler Family Fund, and Promises for Purple to B.M.W. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author contributions

T.H., C.Y., and B.M.W. drafted the manuscript. T.H., C.Y., N.K., V.M.O., A.B., C.S.F., S.O., and B.M.W. planned and conducted the study. All authors collected, analysed, and interpreted the data. M.B.Y., K.P., N.K., V.M.O., A.B., J.A.N., D.A.R., M.G., K.N., P.K., M.J.S., E.L.G., C.S.F., S.O., and B.M.W. edited the manuscript. C.S.F., S.O., and B.M.W. supervised the study. All authors approved the final submitted draft.

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Competing interests

C.S.F. declares consulting for Agios Inc., Bain Capital L.P., Bayer A.G., Celgene Inc., Dicerna Inc., Eli Lilly, Entrinsic Health Solutions Inc., Five Prime Therapeutics Inc., Genentech Inc., Gilead Sciences Inc., KEW Inc., Merck Inc., Merrimack Pharmaceuticals Inc., Pfizer Inc., Sanofi Inc., Taiho Ltd., and Unum Therapeutics Inc. He also serves as a director for CytomX Therapeutics Inc. and owns unexercised stock options for CytomX Therapeutics Inc. and Entrinsic Health Solutions Inc. B.M.W. declares research funding from Celgene Inc., and consulting for BioLineRx Ltd., G1 Therapeutics Inc., and GRAIL Inc. The remaining authors declare no competing interests.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

Informed consent was obtained from all participants at study enrolment, and the HPFS was approved by the institutional review board at Harvard T.H. Chan School of Public Health (Boston, MA, USA). The study was conducted in accordance with the Declaration of Helsinki.


This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Correspondence to Brian M. Wolpin.

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