TY - JOUR
T1 - Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts
AU - Karavasiloglou, Nena
AU - Hughes, David J.
AU - Murphy, Neil
AU - Schomburg, Lutz
AU - Sun, Qian
AU - Seher, Vartiter
AU - Rohrmann, Sabine
AU - Weiderpass, Elisabete
AU - Tjønneland, Anne
AU - Olsen, Anja
AU - Overvad, Kim
AU - Boutron-Ruault, Marie-Christine
AU - Mancini, Francesca Romana
AU - Mahamat-Saleh, Yahya
AU - Kaaks, Rudolf
AU - Kuhn, Tilman
AU - Schulze, Matthias B.
AU - Tumino, Rosario
AU - Panico, Salvatore
AU - Masala, Giovanna
AU - Pala, Valeria
AU - Sacerdote, Carlotta
AU - Derksen, Jeroen W.G.
AU - Skeie, Guri
AU - Hjartåker, Anette
AU - Lasheras, Cristina
AU - Agudo, Antonio
AU - Sánchez, Maria-José
AU - Chirlaque, Maria-Dolores
AU - Ardanaz, Eva
AU - Amiano, Pilar
AU - Van Guelpen, Bethany
AU - Gylling, Björn
AU - Bradbury, Kathryn E.
AU - Papier, Keren
AU - Freisling, Heinz
AU - Aglago, Elom K.
AU - Cross, Amanda J.
AU - Riboli, Elio
AU - Aune, Dagfinn
AU - Gunter, Marc J.
AU - Jenab, Mazda
PY - 2023/1
Y1 - 2023/1
N2 - 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. To explore the association between circulating calcium concentrations and CRC risk using data from 2 large European prospective cohort studies. 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. 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: OR : 0.69; 95% CI: 0.47, 1.00; P-trend = 0.03; UK-BB: OR : 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: OR : 0.63, 95% CI: 0.39, 1.02; P-trend = 0.05; UK-BB: OR : 0.75; 95% CI: 0.64, 0.88; P-trend < 0.01) but not the rectum. 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.
AB - 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. To explore the association between circulating calcium concentrations and CRC risk using data from 2 large European prospective cohort studies. 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. 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: OR : 0.69; 95% CI: 0.47, 1.00; P-trend = 0.03; UK-BB: OR : 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: OR : 0.63, 95% CI: 0.39, 1.02; P-trend = 0.05; UK-BB: OR : 0.75; 95% CI: 0.64, 0.88; P-trend < 0.01) but not the rectum. 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.
U2 - 10.1016/j.ajcnut.2022.10.004
DO - 10.1016/j.ajcnut.2022.10.004
M3 - Article
SN - 0002-9165
VL - 117
SP - 33
EP - 45
JO - The American Journal of Clinical Nutrition
JF - The American Journal of Clinical Nutrition
IS - 1
ER -
