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Vitamin D receptor and calcium-sensing receptor polymorphisms and colorectal cancer survival in the Newfoundland population
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.
Publication titleBritish Journal of Cancer
Department/SchoolMenzies Institute for Medical Research
PublisherNature Publishing Group
Place of publicationMacmillan Building, 4 Crinan St, London, England, N1 9Xw
Rights statementCopyright 2017 Cancer Research UK. All rights reserved. Licensed under Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) https://creativecommons.org/licenses/by-nc-sa/4.0/