Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts

Nena Karavasiloglou; David J Hughes; Neil Murphy; Lutz Schomburg; Qian Sun; Vartiter Seher; Sabine Rohrmann; Elisabete Weiderpass; Anne Tjønneland; Anja Olsen; Kim Overvad; Marie-Christine Boutron-Ruault; Francesca Romana Mancini; Yahya Mahamat-Saleh; Rudolf Kaaks; Tilman Kuhn; Matthias B Schulze; Rosario Tumino; Salvatore Panico; Giovanna Masala; Valeria Pala; Carlotta Sacerdote; Jeroen W G Derksen; Guri Skeie; Anette Hjartåker; Cristina Lasheras; Antonio Agudo; Maria-José Sánchez; Maria-Dolores Chirlaque; Eva Ardanaz; Pilar Amiano; Bethany Van Guelpen; Björn Gylling; Kathryn E Bradbury; Keren Papier; Heinz Freisling; Elom K Aglago; Amanda J Cross; Elio Riboli; Dagfinn Aune; Marc J Gunter; Mazda Jenab

doi:10.1016/j.ajcnut.2022.10.004

Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts

Nena Karavasiloglou, David J Hughes, Neil Murphy, Lutz Schomburg, Qian Sun, Vartiter Seher, Sabine Rohrmann, Elisabete Weiderpass, Anne Tjønneland, Anja Olsen, Kim Overvad, Marie-Christine Boutron-Ruault, Francesca Romana Mancini, Yahya Mahamat-Saleh, Rudolf Kaaks, Tilman Kuhn, Matthias B Schulze, Rosario Tumino, Salvatore Panico, Giovanna MasalaValeria Pala, Carlotta Sacerdote, Jeroen W G Derksen, Guri Skeie, Anette Hjartåker, Cristina Lasheras, Antonio Agudo, Maria-José Sánchez, Maria-Dolores Chirlaque, Eva Ardanaz, Pilar Amiano, Bethany Van Guelpen, Björn Gylling, Kathryn E Bradbury, Keren Papier, Heinz Freisling, Elom K Aglago, Amanda J Cross, Elio Riboli, Dagfinn Aune, Marc J Gunter, Mazda Jenab^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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: 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: OR_Q5vs.Q1: 0.69; 95% CI: 0.47, 1.00; P-trend = 0.03; UK-BB: OR_Q5vs.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: OR_Q5vs.Q1: 0.63, 95% CI: 0.39, 1.02; P-trend = 0.05; UK-BB: OR_Q5vs.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.

Original language	English
Pages (from-to)	33-45
Number of pages	13
Journal	American Journal of Clinical Nutrition
Volume	117
Issue number	1
DOIs	https://doi.org/10.1016/j.ajcnut.2022.10.004
Publication status	Published - Jan 2023

Keywords

cancer
cohort
colorectal
risk
serum calcium

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10.1016/j.ajcnut.2022.10.004

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Karavasiloglou, N., Hughes, D. J., Murphy, N., Schomburg, L., Sun, Q., Seher, V., Rohrmann, S., Weiderpass, E., Tjønneland, A., Olsen, A., Overvad, K., Boutron-Ruault, M.-C., Mancini, F. R., Mahamat-Saleh, Y., Kaaks, R., Kuhn, T., Schulze, M. B., Tumino, R., Panico, S., ... Jenab, M. (2023). Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts. American Journal of Clinical Nutrition, 117(1), 33-45. https://doi.org/10.1016/j.ajcnut.2022.10.004

@article{2b69f31892da4ee492f5a17314f3d758,

title = "Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts",

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: 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.",

keywords = "cancer, cohort, colorectal, risk, serum calcium",

author = "Nena Karavasiloglou and Hughes, {David J} and Neil Murphy and Lutz Schomburg and Qian Sun and Vartiter Seher and Sabine Rohrmann and Elisabete Weiderpass and Anne Tj{\o}nneland and Anja Olsen and Kim Overvad and Marie-Christine Boutron-Ruault and Mancini, {Francesca Romana} and Yahya Mahamat-Saleh and Rudolf Kaaks and Tilman Kuhn and Schulze, {Matthias B} and Rosario Tumino and Salvatore Panico and Giovanna Masala and Valeria Pala and Carlotta Sacerdote and Derksen, {Jeroen W G} and Guri Skeie and Anette Hjart{\aa}ker and Cristina Lasheras and Antonio Agudo and Maria-Jos{\'e} S{\'a}nchez and Maria-Dolores Chirlaque and Eva Ardanaz and Pilar Amiano and {Van Guelpen}, Bethany and Bj{\"o}rn Gylling and Bradbury, {Kathryn E} and Keren Papier and Heinz Freisling and Aglago, {Elom K} and Cross, {Amanda J} and Elio Riboli and Dagfinn Aune and Gunter, {Marc J} and Mazda Jenab",

note = "Publisher Copyright: {\textcopyright} 2022",

year = "2023",

month = jan,

doi = "10.1016/j.ajcnut.2022.10.004",

language = "English",

volume = "117",

pages = "33--45",

journal = "American Journal of Clinical Nutrition",

issn = "0002-9165",

publisher = "Elsevier",

number = "1",

}

Karavasiloglou, N, Hughes, DJ, Murphy, N, Schomburg, L, Sun, Q, Seher, V, Rohrmann, S, Weiderpass, E, Tjønneland, A, Olsen, A, Overvad, K, Boutron-Ruault, M-C, Mancini, FR, Mahamat-Saleh, Y, Kaaks, R, Kuhn, T, Schulze, MB, Tumino, R, Panico, S, Masala, G, Pala, V, Sacerdote, C, Derksen, JWG, Skeie, G, Hjartåker, A, Lasheras, C, Agudo, A, Sánchez, M-J, Chirlaque, M-D, Ardanaz, E, Amiano, P, Van Guelpen, B, Gylling, B, Bradbury, KE, Papier, K, Freisling, H, Aglago, EK, Cross, AJ, Riboli, E, Aune, D, Gunter, MJ & Jenab, M 2023, 'Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts', American Journal of Clinical Nutrition, vol. 117, no. 1, pp. 33-45. https://doi.org/10.1016/j.ajcnut.2022.10.004

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 - 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

UR - http://www.scopus.com/inward/record.url?scp=85148057426&partnerID=8YFLogxK

U2 - 10.1016/j.ajcnut.2022.10.004

DO - 10.1016/j.ajcnut.2022.10.004

M3 - Article

C2 - 36789942

SN - 0002-9165

VL - 117

SP - 33

EP - 45

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 1

ER -

Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts

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