Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients.
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
- Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA USA.
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD USA.
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, VIC Australia.
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY USA.
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA USA.
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON Canada.
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
- Department of Population Science, American Cancer Society, Atlanta, Georgia USA.
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ USA.
- Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX USA.
- Department of Epidemiology, University of Washington, Seattle, WA USA.
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA USA.
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
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.
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