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

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

doi:10.1186/s12885-018-4026-1

Abstract

BackgroundThe 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.MethodsA 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).ResultsThe 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).ConclusionThe 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.

Highlights

The rs2282679 A>C polymorphism in the vitamin D binding protein gene is associated with lower circulating levels of vitamin D
Prior studies on GC variants have been performed on melanoma [21], prostate [22] and breast cancers [23, 24]; we found only two studies that evaluated the specific association of the GC rs2282679 polymorphism with colorectal cancer (CRC) risk, with both studies reporting no evidence of association [25, 26]
We evaluated the potential influence of this single nucleotide polymorphism (SNP) according to dietary vitamin D, calcium, milk, and total dairy product intake and whether associations varied by tumor microsatellite instability (MSI) or BRAF Val600Glu mutation status

Summary

Introduction

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. Colorectal cancer (CRC) is a complex, multifactorial disease resulting from multiple genetic and environmental factors [1]. Vitamin D from diet, supplements, and cutaneous synthesis from sunlight, is associated with lower risks of CRC incidence [2,3,4,5] and mortality [6,7,8,9,10,11]. The anti-carcinogenic effects of vitamin D might vary by the vitamin D-binding protein (DBP) [12]. DBP would be hypothesized to play an important role in CRC initiation and progression, either alone or in combination with vitamin D [18]

Methods

Results

Conclusion