Journal Article

DKFZ-2020-01304

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk.

Zhu, J. ; Shu, X. ; Guo, X. ; Liu, D. ; Bao, J. ; Milne, R. L. ; Giles, G. G. ; Wu, C. ; Du, M. ; White, E. ; Risch, H. A. ; Malats, N. ; Duell, E. J. ; Goodman, P. J. ; Li, D. ; Bracci, P. ; Katzke, V.DKFZ* ; Neale, R. E. ; Gallinger, S. ; Van Den Eeden, S. K. ; Arslan, A. A. ; Canzian, F.DKFZ* ; Kooperberg, C. ; Beane Freeman, L. E. ; Scelo, G. ; Visvanathan, K. ; Haiman, C. A. ; Le Marchand, L. ; Yu, H. ; Petersen, G. M. ; Stolzenberg-Solomon, R. ; Klein, A. P. ; Cai, Q. ; Long, J. ; Shu, X.-O. ; Zheng, W. ; Wu, L.

2020
AACR Philadelphia, Pa.

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Please use a persistent id in citations: doi:10.1158/1055-9965.EPI-20-0091

Abstract: 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 ABO, which has been implicated as a potential target gene of PDAC risk variant. Eight of the identified proteins (LMA2L, TM11D, IP-10, ADH1B, STOM, TENC1, DOCK9, and CRBB2) were associated with PDAC risk after adjusting for previously reported PDAC risk variants (OR ranged from 0.79 to 1.52). Pathway enrichment analysis showed that the encoding genes for implicated proteins were significantly enriched in cancer-related pathways, such as STAT3 and IL15 production.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.

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)
2. C055 Genomische Epidemiologie (C055)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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