Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients

Evertine Wesselink; William Gauderman; Sonja I. Berndt; Hermann Brenner; Daniel D. Buchanan; Peter T. Campbell; Andrew T. Chan; Jenny Chang-Claude; Michelle Cotterchoi; Marc J. Gunter; Michael Hoffmeister; Amit D. Joshi; Christina C. Newton; Rish K. Pai; Andrew J. Pellatt; Amanda I. Phipps; Mingyang Song; Caroline Y. Um; Bethany van Guelpen; Emily White; Ulrike Peters; Fränzel J.B. van Duijnhoven

doi:10.1038/s44276-024-00077-3

Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients

Evertine Wesselink^*, William Gauderman, Sonja I. Berndt, Hermann Brenner, Daniel D. Buchanan, Peter T. Campbell, Andrew T. Chan, Jenny Chang-Claude, Michelle Cotterchoi, Marc J. Gunter, Michael Hoffmeister, Amit D. Joshi, Christina C. Newton, Rish K. Pai, Andrew J. Pellatt, Amanda I. Phipps, Mingyang Song, Caroline Y. Um, Bethany van Guelpen, Emily WhiteUlrike Peters, Fränzel J.B. van Duijnhoven

^*Corresponding author for this work

Nutrition and Disease

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

Abstract

Background
Research on calcium intake as well as variants in the calcium sensor receptor (CaSR) gene and their interaction in relation to CRC survival is still limited.
Methods
Data from 18,952 CRC patients, were included. Associations between primarily pre-diagnostic dietary (n = 13.085), supplemental (n = 11,837), total calcium intake (n = 5970) as well as 325 single nucleotide polymorphisms (SNPs) of the CaSR gene (n = 15,734) in relation to CRC-specific and all-cause mortality were assessed using Cox proportional hazard models. Also interactions between calcium intake and variants in the CaSR gene were assessed.
Results
During a median follow-up of 4.8 years (IQR 2.4–8.4), 6801 deaths occurred, of which 4194 related to CRC. For all-cause mortality, no associations were observed for the highest compared to the lowest sex- and study-specific quartile of dietary (HR 1.00, 95%CI 0.92–1.09), supplemental (HR 0.97, 95%CI 0.89–1.06) and total calcium intake (HR 0.99, 95%CI 0.88–1.11). No associations with CRC-specific mortality were observed either. Interactions were observed between supplemental calcium intake and several SNPs of the CaSR gene.
Conclusion
Calcium intake was not associated with all-cause or CRC-specific mortality in CRC patients. The association between supplemental calcium intake and all-cause and CRC-specific mortality may be modified by genetic variants in the CaSR gene.

Original language	English
Article number	63
Number of pages	12
Journal	BJC Reports
Volume	2
DOIs	https://doi.org/10.1038/s44276-024-00077-3
Publication status	Published - 2 Sept 2024

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Wesselink, E., Gauderman, W., Berndt, S. I., Brenner, H., Buchanan, D. D., Campbell, P. T., Chan, A. T., Chang-Claude, J., Cotterchoi, M., Gunter, M. J., Hoffmeister, M., Joshi, A. D., Newton, C. C., Pai, R. K., Pellatt, A. J., Phipps, A. I., Song, M., Um, C. Y., van Guelpen, B., ... van Duijnhoven, F. J. B. (2024). Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients. BJC Reports, 2, Article 63. https://doi.org/10.1038/s44276-024-00077-3

@article{208bc9b92f4b4d8a904d4a4371d8cee5,

title = "Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients",

abstract = "BackgroundResearch on calcium intake as well as variants in the calcium sensor receptor (CaSR) gene and their interaction in relation to CRC survival is still limited.MethodsData from 18,952 CRC patients, were included. Associations between primarily pre-diagnostic dietary (n = 13.085), supplemental (n = 11,837), total calcium intake (n = 5970) as well as 325 single nucleotide polymorphisms (SNPs) of the CaSR gene (n = 15,734) in relation to CRC-specific and all-cause mortality were assessed using Cox proportional hazard models. Also interactions between calcium intake and variants in the CaSR gene were assessed.ResultsDuring a median follow-up of 4.8 years (IQR 2.4–8.4), 6801 deaths occurred, of which 4194 related to CRC. For all-cause mortality, no associations were observed for the highest compared to the lowest sex- and study-specific quartile of dietary (HR 1.00, 95%CI 0.92–1.09), supplemental (HR 0.97, 95%CI 0.89–1.06) and total calcium intake (HR 0.99, 95%CI 0.88–1.11). No associations with CRC-specific mortality were observed either. Interactions were observed between supplemental calcium intake and several SNPs of the CaSR gene.ConclusionCalcium intake was not associated with all-cause or CRC-specific mortality in CRC patients. The association between supplemental calcium intake and all-cause and CRC-specific mortality may be modified by genetic variants in the CaSR gene.",

author = "Evertine Wesselink and William Gauderman and Berndt, {Sonja I.} and Hermann Brenner and Buchanan, {Daniel D.} and Campbell, {Peter T.} and Chan, {Andrew T.} and Jenny Chang-Claude and Michelle Cotterchoi and Gunter, {Marc J.} and Michael Hoffmeister and Joshi, {Amit D.} and Newton, {Christina C.} and Pai, {Rish K.} and Pellatt, {Andrew J.} and Phipps, {Amanda I.} and Mingyang Song and Um, {Caroline Y.} and {van Guelpen}, Bethany and Emily White and Ulrike Peters and {van Duijnhoven}, {Fr{\"a}nzel J.B.}",

year = "2024",

month = sep,

day = "2",

doi = "10.1038/s44276-024-00077-3",

language = "English",

volume = "2",

journal = "BJC Reports",

issn = "2731-9377",

publisher = "Nature",

}

Wesselink, E, Gauderman, W, Berndt, SI, Brenner, H, Buchanan, DD, Campbell, PT, Chan, AT, Chang-Claude, J, Cotterchoi, M, Gunter, MJ, Hoffmeister, M, Joshi, AD, Newton, CC, Pai, RK, Pellatt, AJ, Phipps, AI, Song, M, Um, CY, van Guelpen, B, White, E, Peters, U & van Duijnhoven, FJB 2024, 'Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients', BJC Reports, vol. 2, 63. https://doi.org/10.1038/s44276-024-00077-3

TY - JOUR

T1 - Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients

AU - Wesselink, Evertine

AU - Gauderman, William

AU - Berndt, Sonja I.

AU - Brenner, Hermann

AU - Buchanan, Daniel D.

AU - Campbell, Peter T.

AU - Chan, Andrew T.

AU - Chang-Claude, Jenny

AU - Cotterchoi, Michelle

AU - Gunter, Marc J.

AU - Hoffmeister, Michael

AU - Joshi, Amit D.

AU - Newton, Christina C.

AU - Pai, Rish K.

AU - Pellatt, Andrew J.

AU - Phipps, Amanda I.

AU - Song, Mingyang

AU - Um, Caroline Y.

AU - van Guelpen, Bethany

AU - White, Emily

AU - Peters, Ulrike

AU - van Duijnhoven, Fränzel J.B.

PY - 2024/9/2

Y1 - 2024/9/2

N2 - BackgroundResearch on calcium intake as well as variants in the calcium sensor receptor (CaSR) gene and their interaction in relation to CRC survival is still limited.MethodsData from 18,952 CRC patients, were included. Associations between primarily pre-diagnostic dietary (n = 13.085), supplemental (n = 11,837), total calcium intake (n = 5970) as well as 325 single nucleotide polymorphisms (SNPs) of the CaSR gene (n = 15,734) in relation to CRC-specific and all-cause mortality were assessed using Cox proportional hazard models. Also interactions between calcium intake and variants in the CaSR gene were assessed.ResultsDuring a median follow-up of 4.8 years (IQR 2.4–8.4), 6801 deaths occurred, of which 4194 related to CRC. For all-cause mortality, no associations were observed for the highest compared to the lowest sex- and study-specific quartile of dietary (HR 1.00, 95%CI 0.92–1.09), supplemental (HR 0.97, 95%CI 0.89–1.06) and total calcium intake (HR 0.99, 95%CI 0.88–1.11). No associations with CRC-specific mortality were observed either. Interactions were observed between supplemental calcium intake and several SNPs of the CaSR gene.ConclusionCalcium intake was not associated with all-cause or CRC-specific mortality in CRC patients. The association between supplemental calcium intake and all-cause and CRC-specific mortality may be modified by genetic variants in the CaSR gene.

AB - BackgroundResearch on calcium intake as well as variants in the calcium sensor receptor (CaSR) gene and their interaction in relation to CRC survival is still limited.MethodsData from 18,952 CRC patients, were included. Associations between primarily pre-diagnostic dietary (n = 13.085), supplemental (n = 11,837), total calcium intake (n = 5970) as well as 325 single nucleotide polymorphisms (SNPs) of the CaSR gene (n = 15,734) in relation to CRC-specific and all-cause mortality were assessed using Cox proportional hazard models. Also interactions between calcium intake and variants in the CaSR gene were assessed.ResultsDuring a median follow-up of 4.8 years (IQR 2.4–8.4), 6801 deaths occurred, of which 4194 related to CRC. For all-cause mortality, no associations were observed for the highest compared to the lowest sex- and study-specific quartile of dietary (HR 1.00, 95%CI 0.92–1.09), supplemental (HR 0.97, 95%CI 0.89–1.06) and total calcium intake (HR 0.99, 95%CI 0.88–1.11). No associations with CRC-specific mortality were observed either. Interactions were observed between supplemental calcium intake and several SNPs of the CaSR gene.ConclusionCalcium intake was not associated with all-cause or CRC-specific mortality in CRC patients. The association between supplemental calcium intake and all-cause and CRC-specific mortality may be modified by genetic variants in the CaSR gene.

U2 - 10.1038/s44276-024-00077-3

DO - 10.1038/s44276-024-00077-3

M3 - Article

SN - 2731-9377

VL - 2

JO - BJC Reports

JF - BJC Reports

M1 - 63

ER -

Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients

Abstract

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