Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk.

Biomarkers, Tumor / metabolism Blood Proteins / metabolism Carcinoma, Pancreatic Ductal / genetics Humans

Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608

Informations de publication

Date de publication:
07 2020
Historique:
received: 17 01 2020
revised: 15 03 2020
accepted: 27 04 2020
pubmed: 23 5 2020
medline: 16 9 2021
entrez: 23 5 2020
Statut: ppublish

Résumé

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with few known risk factors and biomarkers. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers, usually in small samples. In this study, we evaluated associations of circulating protein levels and PDAC risk using genetic instruments. To identify novel circulating protein biomarkers of PDAC, we studied 8,280 cases and 6,728 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium, using genetic instruments of protein quantitative trait loci. We observed associations between predicted concentrations of 38 proteins and PDAC risk at an FDR of < 0.05, including 23 of those proteins that showed an association even after Bonferroni correction. These include the protein encoded by We identified 38 candidates of protein biomarkers for PDAC risk. This study identifies novel protein biomarker candidates for PDAC, which if validated by additional studies, may contribute to the etiologic understanding of PDAC development.

Sections du résumé

BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with few known risk factors and biomarkers. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers, usually in small samples. In this study, we evaluated associations of circulating protein levels and PDAC risk using genetic instruments.
METHODS
To identify novel circulating protein biomarkers of PDAC, we studied 8,280 cases and 6,728 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium, using genetic instruments of protein quantitative trait loci.
RESULTS
We observed associations between predicted concentrations of 38 proteins and PDAC risk at an FDR of < 0.05, including 23 of those proteins that showed an association even after Bonferroni correction. These include the protein encoded by
CONCLUSIONS
We identified 38 candidates of protein biomarkers for PDAC risk.
IMPACT
This study identifies novel protein biomarker candidates for PDAC, which if validated by additional studies, may contribute to the etiologic understanding of PDAC development.

Identifiants

DOI: 10.1158/1055-9965.EPI-20-0091 PMID: 32439797 PMC: PMC7334065
pubmed: 32439797
pii: 1055-9965.EPI-20-0091
doi: 10.1158/1055-9965.EPI-20-0091
pmc: PMC7334065
mid: NIHMS1590964
doi:

Substances chimiques

Biomarkers, Tumor 0
Blood Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1501-1508

Subventions

Organisme : NCI NIH HHS
ID : U10 CA037429
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA218892
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA189974
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600004C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600018C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600001C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100011I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600003C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : K07 CA140790
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600002C
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA154823
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA182883
Pays : United States

Informations de copyright

©2020 American Association for Cancer Research.

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Auteurs

Jingjing Zhu (J)

Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.

Xiang Shu (X)

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
ORCID: 0000-0002-4129-9403

Xingyi Guo (X)

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Duo Liu (D)

Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, China.

Jiandong Bao (J)

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
ORCID: 0000-0003-3423-5118

Roger L Milne (RL)

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
ORCID: 0000-0001-5764-7268

Graham G Giles (GG)

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.

Chong Wu (C)

Department of Statistics, Florida State University, Tallahassee, Florida.

Mengmeng Du (M)

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.

Emily White (E)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Epidemiology, University of Washington, Seattle, Washington.

Harvey A Risch (HA)

Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.

Nuria Malats (N)

Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain.
ORCID: 0000-0003-2538-3784

Eric J Duell (EJ)

Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Spain.
ORCID: 0000-0001-5256-0163

Phyllis J Goodman (PJ)

SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Donghui Li (D)

Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
ORCID: 0000-0002-7542-0662

Paige Bracci (P)

Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.

Verena Katzke (V)

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
ORCID: 0000-0002-6509-6555

Rachel E Neale (RE)

Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Steven Gallinger (S)

Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.

Stephen K Van Den Eeden (SK)

Division of Research, Kaiser Permanente Northern California, Oakland, California.
ORCID: 0000-0002-5599-8387

Alan A Arslan (AA)

Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York.
ORCID: 0000-0002-7775-8085

Federico Canzian (F)

Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
ORCID: 0000-0002-4261-4583

Charles Kooperberg (C)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Laura E Beane Freeman (LE)

Division of Cancer Epidemiology and Genetics, NCI, NIH, Rockville, Maryland.

Ghislaine Scelo (G)

Genetic Epidemiology Group, Section of Genetics, International Agency for Research on Cancer, World Health Organization, Lyon, France.

Kala Visvanathan (K)

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Christopher A Haiman (CA)

Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

Loïc Le Marchand (L)

Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.

Herbert Yu (H)

Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
ORCID: 0000-0003-3950-4815

Gloria M Petersen (GM)

Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.

Rachael Stolzenberg-Solomon (R)

Division of Cancer Epidemiology and Genetics, NCI, NIH, Rockville, Maryland.

Alison P Klein (AP)

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
ORCID: 0000-0003-2737-8399

Qiuyin Cai (Q)

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Jirong Long (J)

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Xiao-Ou Shu (XO)

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
ORCID: 0000-0002-4129-9403

Wei Zheng (W)

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Lang Wu (L)

Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii. lwu@cc.hawaii.edu.

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Associations between Genetically Predicted...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du sang › Associations between Genetically Predicted...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Carcinome du canal pancréatique › Associations between Genetically Predicted...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Associations between Genetically Predicted...