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
Affiliations
Evertine Wesselink
Division of Human Nutrition and Health, Wageningen University & Research
William Gauderman
Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California
Sonja I. Berndt
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
Hermann Brenner
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
Daniel D. Buchanan
Colorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne
Peter T. Campbell
Department of Epidemiology and Population Health, Albert Einstein College of Medicine
Andrew T. Chan
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School
Jenny Chang-Claude
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
Michelle Cotterchoi
Prevention and Cancer Control, Cancer Care Ontario
Marc J. Gunter
Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization
Michael Hoffmeister
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
Amit D. Joshi
Division of Human Nutrition and Health, Wageningen University & Research
Christina C. Newton
Department of Population Science, American Cancer Society
Rish K. Pai
Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona
Andrew J. Pellatt
Department of Cancer Medicine, University of Texas MD Anderson Cancer Center
Amanda I. Phipps
Department of Epidemiology, University of Washington
Mingyang Song
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School
Caroline Y. Um
Department of Population Science, American Cancer Society
Bethany van Guelpen
Department of Radiation Sciences, Oncology Unit, Umeå University
Emily White
Department of Epidemiology, University of Washington
Ulrike Peters
Department of Epidemiology, University of Washington
Fränzel J. B. van Duijnhoven
Division of Human Nutrition and Health, Wageningen University & Research
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.
