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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Association of rs2282679 A>C polymorphism in vitamin D binding protein gene with colorectal cancer risk and survival: effect modification by dietary vitamin D intake

Authors: Yun Zhu, Peizhong Peter Wang, Guangju Zhai, Bharati Bapat, Sevtap Savas, Jennifer R. Woodrow, Peter T. Campbell, Yuming Li, Ning Yang, Xin Zhou, Elizabeth Dicks, John R. Mclaughlin, Patrick S. Parfrey

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

The rs2282679 A>C polymorphism in the vitamin D binding protein gene is associated with lower circulating levels of vitamin D. We investigated associations of this SNP with colorectal cancer (CRC) risk and survival and whether the associations vary by dietary vitamin D intake and tumor molecular phenotype.

Methods

A population-based case-control study identified 637 incident CRC cases (including 489 participants with follow-up data on mortality end-points) and 489 matched controls. Germline DNA samples were genotyped with the Illumina Omni-Quad 1 Million chip in cases and the Affymetrix Axiom® myDesign™ Array in controls. Logistic regression examined the association between the rs2282679 polymorphism and CRC risk with inclusion of potential confounders. Kaplan-Meier curves and multivariable Cox models assessed the polymorphism relative to overall survival (OS) and disease-free survival (DFS).

Results

The rs2282679 polymorphism was not associated with overall CRC risk; there was evidence, however, of effect modification by total vitamin D intake (Pinteraction = 0.019). Survival analyses showed that the C allele was correlated with poor DFS (per-allele HR, 1.36; 95%CI, 1.05–1.77). The association of rs2282679 on DFS was limited to BRAF wild-type tumors (HR, 1.58; 95%CI, 1.12–2.23). For OS, the C allele was associated with higher all-cause mortality among patients with higher levels of dietary vitamin D (HR, 2.11; 95%CI, 1.29–3.74), calcium (HR, 1.93; 95%CI, 1.08–3.46), milk (HR, 2.36; 95%CI, 1.26–4.44), and total dairy product intakes (HR, 2.03; 95%CI, 1.11–3.72).

Conclusion

The rs2282679 SNP was not associated with overall CRC risk, but may be associated with survival after cancer diagnosis. The association of this SNP on survival among CRC patients may differ according to dietary vitamin D and calcium intakes and according to tumor BRAF mutation status.
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Metadata
Title
Association of rs2282679 A>C polymorphism in vitamin D binding protein gene with colorectal cancer risk and survival: effect modification by dietary vitamin D intake
Authors
Yun Zhu
Peizhong Peter Wang
Guangju Zhai
Bharati Bapat
Sevtap Savas
Jennifer R. Woodrow
Peter T. Campbell
Yuming Li
Ning Yang
Xin Zhou
Elizabeth Dicks
John R. Mclaughlin
Patrick S. Parfrey
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4026-1

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