Prediagnostic serum glyceraldehyde-derived advanced glycation end products and mortality among colorectal cancer patients

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  • Ziling Mao
  • Jacqueline Roshelli Baker
  • Masayoshi Takeuchi
  • Hideyuki Hyogo
  • Anne Kirstine Eriksen
  • Gianluca Severi
  • Joseph Rothwell
  • Nasser Laouali
  • Verena Katzke
  • Rudolf Kaaks
  • Matthias B. Schulze
  • Domenico Palli
  • Sabina Sieri
  • Maria Santucci de Magistris
  • Rosario Tumino
  • Carlotta Sacerdote
  • Jeroen W.G. Derksen
  • Inger T. Gram
  • Guri Skeie
  • Torkjel M. Sandanger
  • Jose Ramón Quirós
  • Marta Crous-Bou
  • Maria Jose Sánchez
  • Pilar Amiano
  • Sandra M. Colorado-Yohar
  • Marcela Guevara
  • Sophia Harlid
  • Ingegerd Johansson
  • Aurora Perez-Cornago
  • Heinz Freisling
  • Marc Gunter
  • Elisabete Weiderpass
  • Alicia K. Heath
  • Elom Aglago
  • Mazda Jenab
  • Veronika Fedirko
Glyceraldehyde-derived advanced glycation end products (glycer-AGEs) could contribute to colorectal cancer development and progression due to their pro-oxidative and pro-inflammatory properties. However, the association of glycer-AGEs with mortality after colorectal cancer diagnosis has not been previously investigated. Circulating glycer-AGEs were measured by competitive ELISA. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for associations of circulating glycer-AGEs concentrations with CRC-specific and all-cause mortality among 1034 colorectal cancer (CRC) cases identified within the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1993 and 2013. During a mean of 48 months of follow-up, 529 participants died (409 from CRC). Glycer-AGEs were statistically significantly positively associated with CRC-specific (HRQ5 vs Q1 = 1.53, 95% CI: 1.04-2.25, Ptrend = .002) and all-cause (HRQ5 vs Q1 = 1.62, 95% CI: 1.16-2.26, Ptrend < .001) mortality among individuals with CRC. There was suggestion of a stronger association between glycer-AGEs and CRC-specific mortality among patients with distal colon cancer (per SD increment: HRproximal colon = 1.02, 95% CI: 0.74-1.42; HRdistal colon = 1.51, 95% CI: 1.20-1.91; Peffect modification = .02). The highest HR was observed among CRC cases in the highest body mass index (BMI) and glycer-AGEs category relative to lowest BMI and glycer-AGEs category for both CRC-specific (HR = 1.78, 95% CI: 1.02-3.01) and all-cause mortality (HR = 2.15, 95% CI: 1.33-3.47), although no statistically significant effect modification was observed. Our study found that prediagnostic circulating glycer-AGEs are positively associated with CRC-specific and all-cause mortality among individuals with CRC. Further investigations in other populations and stratifying by tumor location and BMI are warranted.
OriginalsprogEngelsk
TidsskriftInternational Journal of Cancer
Vol/bind152
Udgave nummer11
Sider (fra-til)2257-2268
Antal sider12
ISSN0020-7136
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
: Funding [WCRF 2015/1391, PI: Mazda Jenab] was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam‐Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy, Compagnia di SanPaolo and National Research Council (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), Statistics Netherlands (The Netherlands); 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 Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC‐Norfolk; C8221/A29017 to EPIC‐Oxford), Medical Research Council (1000143 to EPIC‐Norfolk; MR/M012190/1 to EPIC‐Oxford). (United Kingdom). The EPIC‐Norfolk study (doi: 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC‐UU_12015/1) and Cancer Research UK (C864/A14136). Veronika Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Grant support

Funding Information:
We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge, EPIC Asturias and EPIC Aarhus who have enabled this research. We thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study. We would also like to posthumously thank Dr H. Bas Bueno de Mesquita, former Senior Scientist from the RIVM, for his contributions to this work.

Funding Information:
Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award; Wereld Kanker Onderzoek Fonds (WKOF), World Cancer Research Fund International, Grant/Award Number: WCRF 2015/1391; International Agency for Research on Cancer; Imperial College London; NIHR Imperial Biomedical Research Centre; Danish Cancer Society; Ligue Contre le Cancer; Institut Gustave Roussy; Mutuelle Générale de l'Education Nationale; Institut National de la Santé et de la Recherche Médicale; German Cancer Aid; German Cancer Research Center; German Institute of Human Nutrition Potsdam‐Rehbruecke (DIfE); Federal Ministry of Education and Research; Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy; Compagnia di SanPaolo; National Research Council; Dutch Ministry of Public Health; Welfare and Sports (VWS); Registry (NKR), LK Research Funds; Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund; Statistics Netherlands (The Netherlands); Fondo de Investigaciones Sanitarias (FIS; Spanish Health Research Fund); Instituto de Salud Carlos III; Regional Governments of Andalucía; Catalan Institute of Oncology ‐ ICO; Swedish Cancer Society; Swedish Research Council; County Councils of Skåne and Västerbotten; Medical Research Council, Grant/Award Numbers: MC‐UU_12015/1, MR/N003284/1, MR/M012190/1, 1000143; Cancer Research UK, Grant/Award Numbers: C864/A14136, C8221/A29017, 14136; Cancer Prevention and Research Institute of Texas, Grant/Award Number: RR200056 Funding information ε ε δ

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