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 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2021/1/1
Y1 - 2021/1/1
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 -