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. 2017 Sep 5;117(6):898-906.
doi: 10.1038/bjc.2017.242. Epub 2017 Aug 1.

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

Yun Zhu  1   2 , Peizhong Peter Wang  1   2 , Guangju Zhai  3   4 , Bharati Bapat  5 , Sevtap Savas  3   6 , Jennifer R Woodrow  1 , Ishor Sharma  1 , Yuming Li  7 , Xin Zhou  7 , Ning Yang  7 , Peter T Campbell  8 , Elizabeth Dicks  9 , Patrick S Parfrey  9 , John R Mclaughlin  10
Affiliations

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

Yun Zhu et al. Br J Cancer. .

Abstract

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overall survival curves by VDR rs1544410 genotype. Adjusted for age at diagnosis, sex, race, stage at diagnosis, reported screening procedure, marital status, and MSI status.
See this image and copyright information in PMC

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