TY - JOUR
T1 - Genetic and circulating biomarker data improve risk prediction for pancreatic cancer in the general population
AU - Kim, Jihye
AU - Yuan, Chen
AU - Babic, Ana
AU - Bao, Ying
AU - Clish, Clary B.
AU - Pollak, Michael N.
AU - Amundadottir, Laufey T.
AU - Klein, Alison P.
AU - Stolzenberg-Solomon, Rachael Z.
AU - Pandharipande, Pari V.
AU - Brais, Lauren K.
AU - Welch, Marisa W.
AU - Ng, Kimmie
AU - Giovannucci, Edward L.
AU - Sesso, Howard D.
AU - Manson, Jo Ann E.
AU - Stampfer, Meir J.
AU - Fuchs, Charles S.
AU - Wolpin, Brian M.
AU - Kraft, Peter
N1 - Funding Information:
C.S.Fuchs is a consultant for Agios, BainCapital,Taiho, Unum Therapeutics, Daiichi Sankyo, Bayer, Celgene, Eli Lilly, Entrinsic Health, Genentech, Merck, Merrimack Pharma, and Sanofi, and has ownership interest (including patents) in CytomX Therapeutics and Entrinsic Health. B.M. Wolpin is a consultant for Celgene, GRAIL, and BioLineRx, and reports receiving commercial research grants from Celgene and Eli Lilly. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
This project was supported by cohort grants [UM1CA167552 (W. Willett) and U01CA167552 (W. Willet) for the HPFS; UM1CA186107 (M.J. Stampfer), P01CA87969 (R. Tamimi), and R01CA49449 (S. Hankinson) for the Nurses' Health Study; R01CA97193 (J.M. Gaziano), R01CA34944 (C. Hennekens), R01CA40360 (J. Buring), R01HL26490 (C. Hennekens), and R01HL34595 (C. Hennekens) for the PHS; N01WH22110 (R. Prentice), N01WH24152 (N. Lasser), N01WH32100 (S. Beresford), N01WH32101 (R. Grimm), N01WH32102 (R. Wallace), N01WH32105 (A. Oberman), N01WH32106 (E. Paskett), N01WH32108 (P. Greenland), N01WH32109 (J. Manson), N01WH32111 (N. Watts), N01WH32112 (L. Kuller), N01WH32113 (J. Robbins), N01WH32115 (T. Bassford), N01WH32118 (K. Johnson), N01WH32119 (A. Assaf), N01WH32122 (M. Travisan), N01WH42107 (A. Hubbell), N01WH42108 (J. Hsia), N01WH42109 (M. Stefanick), N01WH42110 (J. Hays), N01WH42111 (R. Schenken), N01WH42112 (R. Jackson), N01WH42113 (S. Daugherty), N01WH42114 (C. Ritenbaugh), N01WH42115 (D. Lane), N01WH42116 (J. Ockene), N01WH42117 (G. Heiss), N01WH42118 (S. Hendrix), N01WH42119 (S. Wassertheil-Smoller), N01WH42120 (R. Chiebowski), N01WH42121 (B. Canne), N01WH42122 (J. Kotchen), N01WH42123 (B. Howard), N01WH42124 (H. Black), N01WH42125 (H. Judd), N01WH42126 (J. Liu), N01WH42129 (M. Limacher), N01WH42130 (J. Curb), N01WH42131
Funding Information:
The authors would like to thank the participants and staff of the HPFS, NHS, PHS, and WHI 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, and WY. This project was supported by cohort grants [UM1CA167552 (W. Willett) and U01CA167552 (W. Willet) for the HPFS; UM1CA186107 (M.J. Stampfer), P01CA87969 (R. Tamimi), and R01CA49449 (S. Hankinson) for the Nurses' Health Study; R01CA97193 (J.M. Gaziano), R01CA34944 (C. Hennekens), R01CA40360 (J. Buring), R01HL26490 (C. Hennekens), and R01HL34595 (C. Hennekens) for the PHS; N01WH22110 (R. Prentice), N01WH24152 (N. Lasser), N01WH32100 (S. Beresford), N01WH32101 (R. Grimm), N01WH32102 (R. Wallace), N01WH32105 (A. Oberman), N01WH32106 (E. Paskett), N01WH32108 (P. Greenland), N01WH32109 (J. Manson), N01WH32111 (N. Watts), N01WH32112 (L. Kuller), N01WH32113 (J. Robbins), N01WH32115 (T. Bassford), N01WH32118 (K. Johnson), N01WH32119 (A. Assaf), N01WH32122 (M. Travisan), N01WH42107 (A. Hubbell), N01WH42108 (J. Hsia), N01WH42109 (M. Stefanick), N01WH42110 (J. Hays), N01WH42111 (R. Schenken), N01WH42112 (R. Jackson), N01WH42113 (S. Daugherty), N01WH42114 (C. Ritenbaugh), N01WH42115 (D. Lane), N01WH42116 (J. Ockene), N01WH42117 (G. Heiss), N01WH42118 (S. Hendrix), N01WH42119 (S. Wassertheil-Smoller), N01WH42120 (R. Chiebowski), N01WH42121 (B. Canne), N01WH42122 (J. Kotchen), N01WH42123 (B. Howard), N01WH42124 (H. Black), N01WH42125 (H. Judd), N01WH42126 (J. Liu), N01WH42129 (M. Limacher), N01WH42130 (J. Curb), N01WH42131 (M. O'Sullivan), N01WH42132 (C. Allen), and N01WH44221 (S. Shumaker) for the WHI program] from the NIH. B.M. Wolpin acknowledges primary research support from Dana-Farber Cancer Institute Hale Family Center for Pancreatic Cancer Research, NIH/NCI U01CA210171, Lustgarten Foundation and Stand Up to Cancer, including a Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Interception Translational Cancer Research Grant (Grant Number: SU2C-AACR-DT25-17), with additional support from Pancreatic Action Network, Noble Effort Fund, and Promises for Purple. Stand Up To Cancer is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. K. Ng acknowledges research funding from the Broman Fund for Pancreatic Cancer Research.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/5
Y1 - 2020/5
N2 - Background: Pancreatic cancer is the third leading cause of cancer death in the United States, and 80% of patients present with advanced, incurable disease. Risk markers for pancreatic cancer have been characterized, but combined models are not used clinically to identify individuals at high risk for the disease. Methods: Within a nested case-control study of 500 pancreatic cancer cases diagnosed after blood collection and 1,091 matched controls enrolled in four U.S. prospective cohorts, we characterized absolute risk models that included clinical factors (e.g., body mass index, history of diabetes), germline genetic polymorphisms, and circulating biomarkers. Results: Model discrimination showed an area under ROC curve of 0.62 via cross-validation. Our final integrated model identified 3.7% of men and 2.6% of women who had at least 3 times greater than average risk in the ensuing 10 years. Individuals within the top risk percentile had a 4% risk of developing pancreatic cancer by age 80 years and 2% 10-year risk at age 70 years. Conclusions: Risk models that include established clinical, genetic, and circulating factors improved disease discrimination over models using clinical factors alone. Impact: Absolute risk models for pancreatic cancer may help identify individuals in the general population appropriate for disease interception.
AB - Background: Pancreatic cancer is the third leading cause of cancer death in the United States, and 80% of patients present with advanced, incurable disease. Risk markers for pancreatic cancer have been characterized, but combined models are not used clinically to identify individuals at high risk for the disease. Methods: Within a nested case-control study of 500 pancreatic cancer cases diagnosed after blood collection and 1,091 matched controls enrolled in four U.S. prospective cohorts, we characterized absolute risk models that included clinical factors (e.g., body mass index, history of diabetes), germline genetic polymorphisms, and circulating biomarkers. Results: Model discrimination showed an area under ROC curve of 0.62 via cross-validation. Our final integrated model identified 3.7% of men and 2.6% of women who had at least 3 times greater than average risk in the ensuing 10 years. Individuals within the top risk percentile had a 4% risk of developing pancreatic cancer by age 80 years and 2% 10-year risk at age 70 years. Conclusions: Risk models that include established clinical, genetic, and circulating factors improved disease discrimination over models using clinical factors alone. Impact: Absolute risk models for pancreatic cancer may help identify individuals in the general population appropriate for disease interception.
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UR - http://www.scopus.com/inward/citedby.url?scp=85084932735&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-19-1389
DO - 10.1158/1055-9965.EPI-19-1389
M3 - Article
C2 - 32321713
AN - SCOPUS:85084932735
SN - 1055-9965
VL - 29
SP - 999
EP - 1008
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 5
ER -