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,
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
Affiliations
Yun Zhu
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland
Peizhong Peter Wang
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland
Guangju Zhai
Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland
Bharati Bapat
Department of Laboratory Medicine and Pathobiology, Department of Surgery, University of Toronto
Sevtap Savas
Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland
Jennifer R. Woodrow
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland
Peter T. Campbell
Epidemiology Research Program, American Cancer Society
Yuming Li
Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of Chinese People’s Armed Police Force
Ning Yang
Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of Chinese People’s Armed Police Force
Xin Zhou
Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of Chinese People’s Armed Police Force
Elizabeth Dicks
Clinical Epidemiology Unit, Faculty of Medicine, Memorial University of Newfoundland
John R. Mclaughlin
Division of Epidemiology, Public Health Ontario
Patrick S. Parfrey
Clinical Epidemiology Unit, Faculty of Medicine, Memorial University of Newfoundland
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 (P interaction = 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.
