TY - JOUR
T1 - Soluble receptor for advanced glycation end-products (sRAGE) and colorectal cancer risk
T2 - A case-control study nested within a European prospective cohort
AU - Aglago, Elom K.
AU - Rinaldi, Sabina
AU - Freisling, Heinz
AU - Jiao, Li
AU - Hughes, David J.
AU - Fedirko, Veronika
AU - Schalkwijk, Casper G.
AU - Weiderpass, Elisabete
AU - Dahm, Christina C.
AU - Overvad, Kim
AU - Eriksen, Anne Kirstine
AU - Kyrø, Cecilie
AU - Boutron-Ruault, Marie Christine
AU - Rothwell, Joseph A.
AU - Severi, Gianluca
AU - Katzke, Verena
AU - Kühn, Tilman
AU - Schulze, Matthias B.
AU - Aleksandrova, Krasimira
AU - Masala, Giovanna
AU - Krogh, Vittorio
AU - Panico, Salvatore
AU - Tumino, Rosario
AU - Naccarati, Alessio
AU - Bueno-De-Mesquita, Bas
AU - Van Gils, Carla H.
AU - Sandanger, Torkjel M.
AU - Gram, Inger T.
AU - Skeie, Guri
AU - Quirós, J. Ramón
AU - Jakszyn, Paula
AU - Sánchez, Maria Jose
AU - Amiano, Pilar
AU - Huerta, José María
AU - Ardanaz, Eva
AU - Johansson, Ingegerd
AU - Harlid, Sophia
AU - Perez-Cornago, Aurora
AU - Mayén, Ana Lucia
AU - Cordova, Reynalda
AU - Gunter, Marc J.
AU - Vineis, Paolo
AU - Cross, Amanda J.
AU - Riboli, Elio
AU - Jenab, Mazda
N1 - Funding Information:
The funding for this work (WCRF 2015/1391, to principal investigator, M. Jenab) was obtained from Wereld Kanker Onderzoek Fonds, as part of the World Cancer Research Fund International grant program. The authors thank the EPIC study participants and staff for their valuable contribution to this research. The authors especially thank Mr. Bertrand Hemon and Dr. Aurelie Moskal for their support in
Funding Information:
preparing the databases and providing technical support pertaining to the data analysis, along with Ms. Audrey Brunat-Manquat for her assistance with the laboratory analyses for sRAGE. The coordination of the EPIC study was financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts were supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santéet de la Recherche Médicale (INSERM, France); German Cancer Aid, German Cancer Research Center (DKFZ), and Federal Ministry of Education and Research (BMBF, Germany); Italian Association for Research on Cancer (AIRC), National Research Council, Associa-zione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, and the Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); Health Research Fund (FIS); Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra; the Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública and Instituto de Salud Carlos II (ISCIII RETIC, RD06/0020, Spain); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Ska°ne and V€asterbotten (Sweden); Cancer Research UK, Medical Research
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2021/1
Y1 - 2021/1
N2 - Background: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGEinduced inflammation. Methods: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively. Results: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99). Conclusions: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located withinADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk. Impact: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
AB - Background: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGEinduced inflammation. Methods: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively. Results: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99). Conclusions: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located withinADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk. Impact: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
UR - http://www.scopus.com/inward/record.url?scp=85101026528&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-20-0855
DO - 10.1158/1055-9965.EPI-20-0855
M3 - Article
C2 - 33082206
AN - SCOPUS:85101026528
SN - 1055-9965
VL - 30
SP - 182
EP - 192
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 1
ER -
