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

N1 - Publisher Copyright: © 2022

PY - 2023

Y1 - 2023

N2 - 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: 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.

AB - 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: 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.

KW - cancer

KW - cohort

KW - colorectal

KW - risk

KW - serum calcium

U2 - 10.1016/j.ajcnut.2022.10.004

DO - 10.1016/j.ajcnut.2022.10.004

M3 - Journal article

C2 - 36789942

AN - SCOPUS:85148057426

VL - 117

SP - 33

EP - 45

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

SN - 0002-9165

IS - 1

ER -