Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts
Karavasiloglou, Nena; Hughes, David J; Murphy, Neil; Schomburg, Lutz; Sun, Qian; Seher, Vartiter; Rohrmann, Sabine; Weiderpass, Elisabete; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Mancini, Francesca Romana; Mahamat-Saleh, Yahya; Kaaks, Rudolf; Kuhn, Tilman; Schulze, Matthias B; Tumino, Rosario; Panico, Salvatore; Masala, Giovanna; Pala, Valeria; Sacerdote, Carlotta; Derksen, Jeroen W G; Skeie, Guri; Hjartåker, Anette; Lasheras, Cristina; Agudo, Antonio; Sánchez, Maria-José; Chirlaque, Maria-Dolores; Ardanaz, Eva; Amiano, Pilar; Van Guelpen, Bethany; Gylling, Björn; Bradbury, Kathryn E; Papier, Keren; Freisling, Heinz; Aglago, Elom K; Cross, Amanda J; Riboli, Elio; Aune, Dagfinn; Gunter, Marc J; Jenab, Mazda
(2023) American Journal of Clinical Nutrition, volume 117, issue 1, pp. 33 - 45
(Article)
Abstract
Background: Higher dietary calcium consumption is associated with lower colorectal cancer (CRC) risk. However, little data are available on the association between circulating calcium concentrations and CRC risk. Objectives: To explore the association between circulating calcium concentrations and CRC risk using data from 2 large European prospective cohort studies. Methods:
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Conditional logistic regression models were used to calculate multivariable-adjusted ORs and 95% CIs in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC; n-cases = 947, n-controls = 947) and the UK Biobank (UK-BB; n-cases = 2759, n-controls = 12,021) cohorts. Results: In EPIC, nonalbumin-adjusted total serum calcium (a proxy of free calcium) was not associated with CRC (OR: 0.94; 95% CI: 0.85, 1.03; modeled as continuous variable, per 1 mg/dL increase), colon cancer (OR: 0.93; 95% CI: 0.82, 1.05) or rectal cancer (OR: 1.01; 95% CI: 0.84, 1.20) risk in the multivariable adjusted model. In the UK-BB, serum ionized calcium (free calcium, most active form) was inversely associated with the risk of CRC (OR: 0.85; 95% CI: 0.76, 0.95; per 1 mg/dL) and colon cancer (OR: 0.78; 95% CI: 0.68, 0.90), but not rectal cancer (OR: 1.02; 95% CI: 0.83, 1.24) in multivariable adjusted models. Meta-analysis of EPIC and UK-BB CRC risk estimates showed an inverse risk association for CRC in the multivariable adjusted model (OR: 0.90; 95%CI: 0.84, 0.97). In analyses by quintiles, in both cohorts, higher levels of serum calcium were associated with reduced CRC risk (EPIC: ORQ5vs.Q1: 0.69; 95% CI: 0.47, 1.00; P-trend = 0.03; UK-BB: ORQ5vs.Q1: 0.82; 95% CI: 0.72, 0.94; P-trend < 0.01). Analyses by anatomical subsite showed an inverse cancer risk association in the colon (EPIC: ORQ5vs.Q1: 0.63, 95% CI: 0.39, 1.02; P-trend = 0.05; UK-BB: ORQ5vs.Q1: 0.75; 95% CI: 0.64, 0.88; P-trend < 0.01) but not the rectum. Conclusions: In UK-BB, higher serum ionized calcium levels were inversely associated with CRC, but the risk was restricted to the colon. Total serum calcium showed a null association in EPIC. Additional prospective studies in other populations are needed to better investigate these associations.
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Keywords: cancer, cohort, colorectal, risk, serum calcium, Nutrition and Dietetics, Medicine (miscellaneous)
ISSN: 0002-9165
Publisher: American Society for Nutrition
Note: Publisher Copyright: © 2022
(Peer reviewed)