Sex‐ and site‐specific associations of circulating lipocalin 2 and incident colorectal cancer: Results from the <scp>EPIC</scp> cohort

Experimental research has uncovered lipocalin 2 (LCN2) as a novel biomarker implicated in the modulation of intestinal inflammation, metabolic homeostasis, and colon carcinogenesis. However, evidence from human research has been scant. We, therefore, explored the association of pre-diagnostic circulating LCN2 concentrations with incident colorectal cancer (CRC) in a nested case-control study within the in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. LCN2 was measured in 1267 incident CRC cases matched to 1267 controls using incidence density sampling. Conditional logistic regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) according to tumor subsite and sex. Weighted Cox proportional hazard regression was used to explore associations by adiposity status. In multivariable-adjusted analyses, the IRR [95% CI] per doubling in LCN2 concentration was 1.16 [0.98-1.37] for CRC overall, 1.26 [1.00-1.59] for colon cancer, and 1.08 [0.85-1.38] for rectal cancer. The association for colon cancer was more pronounced in women (IRR [95% CI], 1.66 [1.20-2.30]) and for proximal colon cancer (IRR [95% CI], 1.96 [1.15-3.34]), whereas no association was seen in men and distal colon cancer. The association for colon cancer was positive in individuals with high waist circumference (hazard ratio [95% CI], 1.69 [1.52-1.88]) and inverse in individuals with low waist circumference (hazard ratio [95% CI], 0.86 [0.76-0.98], P interaction<0.01). Overall, these data suggest that pre-diagnostic LCN2 concentrations were positively associated with colon cancer, particularly occurring in the proximal colon, in women and among individuals with abdominal adiposity.

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Journal
International Journal of Cancer
Published
2024-11-07
DOI
https://doi.org/10.1002/ijc.35205
Citations
3
Primary Topic
Electrolyte and hormonal disorders
Type
article
Field-Weighted Citation Impact
1.26

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article

Sex‐ and site‐specific associations of circulating lipocalin 2 and incident colorectal cancer: Results from the EPIC cohort

Fabrizio Pasanisi, Alicia K. Heath, Paula Jakszyn, Krasimira Aleksandrova et al.
3 citations
International Journal of Cancer
Electrolyte and hormonal disorders
1.26
article

Sex‐ and site‐specific associations of circulating lipocalin 2 and incident colorectal cancer: Results from the EPIC cohort

Fabrizio Pasanisi, Alicia K. Heath, Paula Jakszyn, Krasimira Aleksandrova, Bethany Van Guelpen, Rudolf Kaaks, Joseph A. Rothwell, Matthias Bernd Schulze, ­Rosario ­Tumino, Mazda Jenab, Robin Reichmann, Sabina Sieri, Fabian Eichelmann, Giovanna Masala, Tobias Pischon, Marcela Guevara, Verena Katzke, Karl Smith‐Byrne, Elom K. Aglago, Marc J. Gunter, Sandra M. Colorado‐Yohar, Jürgen Janke, Pilar Amiano, Elisabete Weiderpass, Anne Marie Tjønneland, Anne Kirstine Eriksen, Katharina Nimptsch, Marı́a Teresa Giraudo, Gianluca Severi, María‐José Sánchez
article en
3 citations

Abstract

Experimental research has uncovered lipocalin 2 (LCN2) as a novel biomarker implicated in the modulation of intestinal inflammation, metabolic homeostasis, and colon carcinogenesis. However, evidence from human research has been scant. We, therefore, explored the association of pre-diagnostic circulating LCN2 concentrations with incident colorectal cancer (CRC) in a nested case-control study within the in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. LCN2 was measured in 1267 incident CRC cases matched to 1267 controls using incidence density sampling. Conditional logistic regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) according to tumor subsite and sex. Weighted Cox proportional hazard regression was used to explore associations by adiposity status. In multivariable-adjusted analyses, the IRR [95% CI] per doubling in LCN2 concentration was 1.16 [0.98-1.37] for CRC overall, 1.26 [1.00-1.59] for colon cancer, and 1.08 [0.85-1.38] for rectal cancer. The association for colon cancer was more pronounced in women (IRR [95% CI], 1.66 [1.20-2.30]) and for proximal colon cancer (IRR [95% CI], 1.96 [1.15-3.34]), whereas no association was seen in men and distal colon cancer. The association for colon cancer was positive in individuals with high waist circumference (hazard ratio [95% CI], 1.69 [1.52-1.88]) and inverse in individuals with low waist circumference (hazard ratio [95% CI], 0.86 [0.76-0.98], P interaction<0.01). Overall, these data suggest that pre-diagnostic LCN2 concentrations were positively associated with colon cancer, particularly occurring in the proximal colon, in women and among individuals with abdominal adiposity.

International Journal of CancerVol. 156(5)
University of Copenhagen (DK), Inserm (FR), Universidad de Granada (ES), University of Potsdam (DE), German Cancer Research Center (DE), University of Bremen (DE), Université de Versailles Saint-Quentin-en-Yvelines (FR), Max Delbrück Center (DE), Heidelberg University (DE), Basque Government (ES), Instituto de Salud Carlos III (ES), Prevention Institute (US), Universidad de Antioquia (CO), Humboldt-Universität zu Berlin (DE), University of Oxford (GB), Instituto de Salud Pública de Navarra (ES), Ministry of Health (ES), Biogipuzkoa Health Research Institute (ES), Centre de recherche en Epidémiologie et Santé des Populations (FR), Institut Català d'Oncologia (ES), Navarre Institute of Health Research (ES), Instituto de Investigación Biosanitaria de Granada (ES), Leibniz Institute for Prevention Research and Epidemiology - BIPS (DE), Federico II University Hospital (IT), Italian Association for Cancer Research (IT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), Instituto Murciano de Investigación Biosanitaria (ES), Danish Cancer Society (DK), Deutsches Diabetes-Zentrum e.V. (DE), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), German Center for Diabetes Research (DE), German Institute of Human Nutrition (DE), Centre international de recherche sur le cancer (FR), Heinrich Heine University Düsseldorf (DE), University of Florence (IT), Imperial College London (GB), University of Turin (IT), Universitat Ramon Llull (ES), Andalusian School of Public Health (ES), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE), Umeå University (SE)
Aarhus Universitet, Kræftens Bekæmpelse, Universiteit Utrecht, Bundesministerium für Bildung und Forschung, Cancerfonden, Ligue Contre le Cancer, Deutsche Krebshilfe, Medical Research Council, Instituto de Salud Carlos III, Rijksinstituut voor Volksgezondheid en Milieu
Good health and well-being
Openalex Percentile: Top 18%
Electrolyte and hormonal disorders
1.26
DOIOpen Access PDFOpenAlex
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