TY - JOUR
T1 - Associations between genetically predicted blood protein biomarkers and pancreatic cancer risk
AU - Zhu, Jingjing
AU - Shu, Xiang
AU - Guo, Xingyi
AU - Liu, Duo
AU - Bao, Jiandong
AU - Milne, Roger L.
AU - Giles, Graham G.
AU - Wu, Chong
AU - Du, Mengmeng
AU - White, Emily
AU - Risch, Harvey A.
AU - Malats, Nuria
AU - Duell, Eric J.
AU - Goodman, Phyllis J.
AU - Li, Donghui
AU - Bracci, Paige
AU - Katzke, Verena
AU - Neale, Rachel E.
AU - Gallinger, Steven
AU - van Den Eeden, Stephen K.
AU - Arslan, Alan A.
AU - Canzian, Federico
AU - Kooperberg, Charles
AU - Beane Freeman, Laura E.
AU - Scelo, Ghislaine
AU - Visvanathan, Kala
AU - Haiman, Christopher A.
AU - Le Marchand, Loc
AU - Yu, Herbert
AU - Petersen, Gloria M.
AU - Stolzenberg-Solomon, Rachael
AU - Klein, Alison P.
AU - Cai, Qiuyin
AU - Long, Jirong
AU - Shu, Xiao Ou
AU - Zheng, Wei
AU - Wu, Lang
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/7
Y1 - 2020/7
N2 - 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 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. 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.
AB - 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 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. 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.
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U2 - 10.1158/1055-9965.EPI-20-0091
DO - 10.1158/1055-9965.EPI-20-0091
M3 - Article
C2 - 32439797
AN - SCOPUS:85087530278
SN - 1055-9965
VL - 29
SP - 1501
EP - 1508
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 7
ER -