{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:30:51Z","timestamp":1786559451615,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA154823"],"award-info":[{"award-number":["R01CA154823"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["SP\/09\/002"],"award-info":[{"award-number":["SP\/09\/002"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/13\/13\/30194"],"award-info":[{"award-number":["RG\/13\/13\/30194"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/18\/13\/33946"],"award-info":[{"award-number":["RG\/18\/13\/33946"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pancreatic ductal adenocarcinoma (PDAC) represents a highly fatal malignancy with a huge public health burden. There is a critical need to better understand its etiology for developing innovative strategies for effective prevention and treatment. Leveraging genetic variants as instrumental variables, Mendelian randomization and proteome\u2010wide association study have identified dozens of protein biomarkers associated with PDAC risk, yet potential nonlinear associations have largely been underexplored. In this study, we applied a nonlinear modeling approach, combining two\u2010stage sliced inverse regression (2SIR) with nonlinear transformations via adjusted inverse regression (AIR), to investigate associations between genetically predicted protein concentrations in plasma and PC risk, by integrating blood proteome and genome data from the INTERVAL study (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093301), and a large genome\u2010wide association study of PC risk (8275 cases and 6723 controls). We identified 25 genetically predicted proteins associated with PDAC risk after multiple comparison correction, including 22 that had been previously reported using linear modeling methods, and an additional three novel proteins (APOF, CCL15, and CHIT1). Importantly, there has been some level of evidence in the literature supporting potentially important roles of some of these novel proteins in PDAC development. Our study underscores the importance of accounting for nonlinear relationships in uncovering novel proteins associated with PDAC risk. If validated in further studies, our findings could improve the understanding of PDAC pathogenesis and inform future therapeutic and risk assessment strategies to reduce the burden from this deadly cancer.\n                  <\/jats:p>","DOI":"10.1002\/mc.70135","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:36:11Z","timestamp":1780378571000},"page":"1025-1032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nonlinear Modeling Reveals Novel Associations Between Genetically Predicted Protein Levels and Pancreatic Cancer Risk"],"prefix":"10.1002","volume":"65","author":[{"given":"Jingjing","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Interdisciplinary Oncology and Department of Genetics, LSU\u2010LCMC Health Cancer Center, School of Medicine Louisiana State University Health Sciences Center New Orleans Louisiana USA"},{"name":"Bioinformatics and Genomics Core, School of Medicine Louisiana State University Health Sciences Center New Orleans Louisiana USA"},{"name":"Department of Quantitative Health Sciences, John A. Burns School of Medicine University of Hawai'i at M\u0101noa Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of Texas MD Anderson Cancer Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omeed","family":"Moaven","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery LSU New Orleans School of Medicine New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, Section of Clinical Epidemiology, Graduate School of Medicine Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Statistics The Chinese University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology and Department of Genetics, LSU\u2010LCMC Health Cancer Center, School of Medicine Louisiana State University Health Sciences Center New Orleans Louisiana USA"},{"name":"Epidemiology and Population Health Program, School of Public Health LSU\u2010Health Sciences Center New Orleans Louisiana USA"},{"name":"Population Sciences in the Pacific Program, University of Hawai'i Cancer Center University of Hawai'i at M\u0101noa Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.14740\/wjon1166"},{"key":"e_1_2_11_3_1","first-page":"105","article-title":"The Clinical Utility of Serum CA 19\u20109 in the Diagnosis, Prognosis and Management of Pancreatic Adenocarcinoma: An Evidence Based Appraisal","volume":"3","author":"Ballehaninna U. 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