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

BJC Rep. 2024;2(1):63. doi: 10.1038/s44276-024-00077-3. Epub 2024 Sep 2.

Authors

Evertine Wesselink¹, William Gauderman², Sonja I Berndt³, Hermann Brenner^{4

5

6}, Daniel D Buchanan^{7

8

9}, Peter T Campbell¹⁰, Andrew T Chan^{11

12

13

14

15}, Jenny Chang-Claude^{16

17}, Michelle Cotterchoi^{18

19}, Marc J Gunter^{20

21}, Michael Hoffmeister⁴, Amit D Joshi^{1

13

15}, Christina C Newton²², Rish K Pai²³, Andrew J Pellatt²⁴, Amanda I Phipps^{25

26}, Mingyang Song^{13

27}, Caroline Y Um²², Bethany van Guelpen^{28

29}, Emily White^{25

26}, Ulrike Peters^{25

26}, Fränzel J B van Duijnhoven¹

Affiliations

¹ Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
² Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA USA.
³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD USA.
⁴ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵ Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
⁶ German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁷ Colorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, VIC Australia.
⁸ University of Melbourne Centre for Cancer Research, The University of Melbourne, Parkville, VIC Australia.
⁹ Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC Australia.
¹⁰ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY USA.
¹¹ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA USA.
¹² Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA USA.
¹³ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA USA.
¹⁴ Broad Institute of Harvard and MIT, Cambridge, MA USA.
¹⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA USA.
¹⁶ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁷ University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
¹⁸ Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON Canada.
¹⁹ Dalla Lana School of Public Health, University of Toronto, Toronto, ON Canada.
²⁰ Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
²¹ Department of Epidemiology and Biostatistics School of Public Health Imperial College London, London, UK.
²² Department of Population Science, American Cancer Society, Atlanta, Georgia USA.
²³ Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ USA.
²⁴ Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX USA.
²⁵ Department of Epidemiology, University of Washington, Seattle, WA USA.
²⁶ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA USA.
²⁷ Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA USA.
²⁸ Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
²⁹ Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.

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.

Abstract

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