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

Author:

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

Abstract

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.

Funder

National Institutes of Health

German Research Council

VicHealth and Cancer Council Victoria

The American Cancer Society

National Cancer Institute, United States

International Agency for Research on Cancer

NIHR Imperial Biomedical Research Centre

National Institute of Health, United States

Swedish Research Council

Swedish Cancer Society

Region Västerbotten

Knut och Alice Wallenbergs Stiftelse

Publisher

Springer Science and Business Media LLC

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