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Vitamin D receptor and calcium-sensing receptor polymorphisms and colorectal cancer survival in the Newfoundland population


Zhu, Y and Wang, PP and Zhai, G and Bapat, B and Savas, S and Woodrow, JR and Sharma, I and Li, Y and Zhou, X and Yang, N and Campbell, PT and Dicks, E and Parfrey, PS and McLaughlin, JR, Vitamin D receptor and calcium-sensing receptor polymorphisms and colorectal cancer survival in the Newfoundland population, British Journal of Cancer, 117, (6) pp. 898-906. ISSN 0007-0920 (2017) [Refereed Article]

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Copyright 2017 Cancer Research UK. All rights reserved. Licensed under Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)

DOI: doi:10.1038/bjc.2017.242


Background: Increased serum levels of vitamin D and calcium have been associated with lower risks of colorectal cancer (CRC) incidence and mortality. These inverse associations may be mediated by the vitamin D receptor (VDR) and the calcium-sensing receptor (CASR). We investigated genetic variants in VDR and CASR for their relevance to CRC prognosis.

Methods: A population-based cohort of 531 CRC patients diagnosed from 1999 to 2003 in Newfoundland and Labrador, Canada, was followed for mortality and cancer recurrence until April 2010. Germline DNA samples were genotyped with the Illumina Omni-Quad 1 Million chip. Multivariate Cox models assessed 41 tag single-nucleotide polymorphisms and relative haplotypes on VDR and CASR in relation to all-cause mortality (overall survival, OS) and disease-free survival (DFS).

Results: Gene-level associations were observed between VDR and the DFS of rectal cancer patients (P = 0.037) as well as between CASR and the OS of colon cancer patients (P = 0.014). Haplotype analysis within linkage blocks of CASR revealed the G-G-G-G-G-A-C haplotype (rs10222633-rs10934578-rs3804592-rs17250717-A986S-R990G-rs1802757) to be associated with a decreased OS of colon cancer (HR, 3.15; 95% CI, 1.66-5.96). Potential interactions were seen among prediagnostic dietary calcium intake with the CASR R990G (Pint = 0.040) and the CASR G-T-G-G-G-G-C haplotype for rs10222633-rs10934578-rs3804592-rs17250717-A986S-R990G-rs1802757 (Pint = 0.017), with decreased OS time associated with these variants limited to patients consuming dietary calcium below the median, although the stratified results were not statistically significant after correction for multiple testing.

Conclusions: Polymorphic variations in VDR and CASR may be associated with survival after a diagnosis of CRC.

Item Details

Item Type:Refereed Article
Keywords:vitamin D receptor, calcium sensing receptor, polymorphism, gene-environment interaction, colorectal cancer survival
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Rheumatology and arthritis
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Zhai, G (Dr Guangju Zhai)
ID Code:123193
Year Published:2017
Web of Science® Times Cited:12
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-12-20
Last Modified:2018-06-26

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