Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer

Lina Zgaga; Evropi Theodoratou; Susan M Farrington; Farhat V N Din; Li Yin Ooi; Dominik Glodzik; Susan Johnston; Albert Tenesa; Harry Campbell; Malcolm G Dunlop

doi:10.1200/JCO.2013.54.5947

Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer

Lina Zgaga, Evropi Theodoratou, Susan M Farrington, Farhat V N Din, Li Yin Ooi, Dominik Glodzik, Susan Johnston, Albert Tenesa, Harry Campbell, Malcolm G Dunlop

Research output: Contribution to journal › Article › peer-review

Abstract

Purpose: We investigated whether the plasma level of 25-hydroxyvitamin D (25-OHD) after a diagnosis of colorectal cancer (CRC) influences survival outcome.

Patients and Methods: We prospectively studied 1,598 patients with stage I to III CRC. We sought association between plasma 25-OHD and stage-specific survival and tested for interaction between 25-OHD level and variation at the vitamin D receptor (VDR) gene locus. Blood was sampled postoperatively, and plasma was assayed for 25-OHD by liquid chromatography-tandem mass spectrometry. VDR polymorphisms (rs1544410, rs10735810, rs7975232, rs11568820) were genotyped, and haplotypes were inferred by using BEAGLE software. We tested for association between survival and 25-OHD, VDR genotype/haplotype, and after applying a VDR genotype–25-OHD interaction term. We conducted Kaplan-Meier survival analysis and used Cox proportional hazards models to estimate adjusted hazard ratios (HRs).

Results: We found strong associations between plasma 25-OHD concentration and CRC-specific (P = .008) and all-cause mortality (P = .003). Adjusted HRs were 0.68 (95% CI, 0.50 to 0.90) and 0.70 (95% CI, 0.55 to 0.89), respectively (highest v lowest 25-OHD tertile), particularly in stage II disease (HR, 0.44; P = .004 for CRC-specific mortality). We detected gene-environment interactions between 25-OHD concentration and rs11568820 genotype for CRC-specific (P = .008) and all-cause (P = .022) mortality, number of protective alleles (P = .004 and P = .018, respectively), and GAGC haplotype at the VDR locus for all-cause mortality (P = .008).

Conclusion: In patients with stage I to III CRC, postoperative plasma vitamin D is associated with clinically important differences in survival outcome, higher levels being associated with better outcome. We observed interactions between 25-OHD level and VDR genotype, suggesting a causal relationship between vitamin D and survival. The influence of vitamin D supplementation on CRC outcome will require further investigation.

Original language	English
Pages (from-to)	2430-2439
Number of pages	10
Journal	Journal of Clinical Oncology
Volume	32
Issue number	23
Early online date	7 Jul 2014
DOIs	https://doi.org/10.1200/JCO.2013.54.5947
Publication status	Published - 10 Aug 2014

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Statistical and computational methods for population stratification and prediction of cancer risk
Tenesa, A.
UK-based charities
1/10/11 → 31/05/15
Project: Research

Harry Campbell
- Deanery of Molecular, Genetic and Population Health Sciences - Personal Chair of Genetic Epidemiology & Public Health
- Global Health Academy
- Usher Institute
- Centre for Global Health Research
Person: Academic: Research Active
Farhat Din
- Deanery of Molecular, Genetic and Population Health Sciences - Senior Clinical Lecturer
- Edinburgh Cancer Research Centre
Person: Academic: Research Active
Malcolm Dunlop
- Deanery of Molecular, Genetic and Population Health Sciences - Chair of Coloproctology
- Edinburgh Cancer Research Centre
Person: Academic: Research Active

Cite this

@article{a76d764af7be4d03a28b8741050f462a,

title = "Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer",

abstract = "Purpose: We investigated whether the plasma level of 25-hydroxyvitamin D (25-OHD) after a diagnosis of colorectal cancer (CRC) influences survival outcome.Patients and Methods: We prospectively studied 1,598 patients with stage I to III CRC. We sought association between plasma 25-OHD and stage-specific survival and tested for interaction between 25-OHD level and variation at the vitamin D receptor (VDR) gene locus. Blood was sampled postoperatively, and plasma was assayed for 25-OHD by liquid chromatography-tandem mass spectrometry. VDR polymorphisms (rs1544410, rs10735810, rs7975232, rs11568820) were genotyped, and haplotypes were inferred by using BEAGLE software. We tested for association between survival and 25-OHD, VDR genotype/haplotype, and after applying a VDR genotype–25-OHD interaction term. We conducted Kaplan-Meier survival analysis and used Cox proportional hazards models to estimate adjusted hazard ratios (HRs).Results: We found strong associations between plasma 25-OHD concentration and CRC-specific (P = .008) and all-cause mortality (P = .003). Adjusted HRs were 0.68 (95% CI, 0.50 to 0.90) and 0.70 (95% CI, 0.55 to 0.89), respectively (highest v lowest 25-OHD tertile), particularly in stage II disease (HR, 0.44; P = .004 for CRC-specific mortality). We detected gene-environment interactions between 25-OHD concentration and rs11568820 genotype for CRC-specific (P = .008) and all-cause (P = .022) mortality, number of protective alleles (P = .004 and P = .018, respectively), and GAGC haplotype at the VDR locus for all-cause mortality (P = .008).Conclusion: In patients with stage I to III CRC, postoperative plasma vitamin D is associated with clinically important differences in survival outcome, higher levels being associated with better outcome. We observed interactions between 25-OHD level and VDR genotype, suggesting a causal relationship between vitamin D and survival. The influence of vitamin D supplementation on CRC outcome will require further investigation.",

author = "Lina Zgaga and Evropi Theodoratou and Farrington, {Susan M} and Din, {Farhat V N} and Ooi, {Li Yin} and Dominik Glodzik and Susan Johnston and Albert Tenesa and Harry Campbell and Dunlop, {Malcolm G}",

note = "{\textcopyright}American Society of Clinical Oncology.",

year = "2014",

month = aug,

day = "10",

doi = "10.1200/JCO.2013.54.5947",

language = "English",

volume = "32",

pages = "2430--2439",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "23",

}

Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer. / Zgaga, Lina; Theodoratou, Evropi ; Farrington, Susan M ; Din, Farhat V N; Ooi, Li Yin; Glodzik, Dominik; Johnston, Susan; Tenesa, Albert ; Campbell, Harry ; Dunlop, Malcolm G.

In: Journal of Clinical Oncology, Vol. 32, No. 23, 10.08.2014, p. 2430-2439.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer

AU - Zgaga, Lina

AU - Theodoratou, Evropi

AU - Farrington, Susan M

AU - Din, Farhat V N

AU - Ooi, Li Yin

AU - Glodzik, Dominik

AU - Johnston, Susan

AU - Tenesa, Albert

AU - Campbell, Harry

AU - Dunlop, Malcolm G

PY - 2014/8/10

Y1 - 2014/8/10

N2 - Purpose: We investigated whether the plasma level of 25-hydroxyvitamin D (25-OHD) after a diagnosis of colorectal cancer (CRC) influences survival outcome.Patients and Methods: We prospectively studied 1,598 patients with stage I to III CRC. We sought association between plasma 25-OHD and stage-specific survival and tested for interaction between 25-OHD level and variation at the vitamin D receptor (VDR) gene locus. Blood was sampled postoperatively, and plasma was assayed for 25-OHD by liquid chromatography-tandem mass spectrometry. VDR polymorphisms (rs1544410, rs10735810, rs7975232, rs11568820) were genotyped, and haplotypes were inferred by using BEAGLE software. We tested for association between survival and 25-OHD, VDR genotype/haplotype, and after applying a VDR genotype–25-OHD interaction term. We conducted Kaplan-Meier survival analysis and used Cox proportional hazards models to estimate adjusted hazard ratios (HRs).Results: We found strong associations between plasma 25-OHD concentration and CRC-specific (P = .008) and all-cause mortality (P = .003). Adjusted HRs were 0.68 (95% CI, 0.50 to 0.90) and 0.70 (95% CI, 0.55 to 0.89), respectively (highest v lowest 25-OHD tertile), particularly in stage II disease (HR, 0.44; P = .004 for CRC-specific mortality). We detected gene-environment interactions between 25-OHD concentration and rs11568820 genotype for CRC-specific (P = .008) and all-cause (P = .022) mortality, number of protective alleles (P = .004 and P = .018, respectively), and GAGC haplotype at the VDR locus for all-cause mortality (P = .008).Conclusion: In patients with stage I to III CRC, postoperative plasma vitamin D is associated with clinically important differences in survival outcome, higher levels being associated with better outcome. We observed interactions between 25-OHD level and VDR genotype, suggesting a causal relationship between vitamin D and survival. The influence of vitamin D supplementation on CRC outcome will require further investigation.

AB - Purpose: We investigated whether the plasma level of 25-hydroxyvitamin D (25-OHD) after a diagnosis of colorectal cancer (CRC) influences survival outcome.Patients and Methods: We prospectively studied 1,598 patients with stage I to III CRC. We sought association between plasma 25-OHD and stage-specific survival and tested for interaction between 25-OHD level and variation at the vitamin D receptor (VDR) gene locus. Blood was sampled postoperatively, and plasma was assayed for 25-OHD by liquid chromatography-tandem mass spectrometry. VDR polymorphisms (rs1544410, rs10735810, rs7975232, rs11568820) were genotyped, and haplotypes were inferred by using BEAGLE software. We tested for association between survival and 25-OHD, VDR genotype/haplotype, and after applying a VDR genotype–25-OHD interaction term. We conducted Kaplan-Meier survival analysis and used Cox proportional hazards models to estimate adjusted hazard ratios (HRs).Results: We found strong associations between plasma 25-OHD concentration and CRC-specific (P = .008) and all-cause mortality (P = .003). Adjusted HRs were 0.68 (95% CI, 0.50 to 0.90) and 0.70 (95% CI, 0.55 to 0.89), respectively (highest v lowest 25-OHD tertile), particularly in stage II disease (HR, 0.44; P = .004 for CRC-specific mortality). We detected gene-environment interactions between 25-OHD concentration and rs11568820 genotype for CRC-specific (P = .008) and all-cause (P = .022) mortality, number of protective alleles (P = .004 and P = .018, respectively), and GAGC haplotype at the VDR locus for all-cause mortality (P = .008).Conclusion: In patients with stage I to III CRC, postoperative plasma vitamin D is associated with clinically important differences in survival outcome, higher levels being associated with better outcome. We observed interactions between 25-OHD level and VDR genotype, suggesting a causal relationship between vitamin D and survival. The influence of vitamin D supplementation on CRC outcome will require further investigation.

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DO - 10.1200/JCO.2013.54.5947

M3 - Article

C2 - 25002714

VL - 32

SP - 2430

EP - 2439

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 23

ER -

Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer

Abstract

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Statistical and computational methods for population stratification and prediction of cancer risk

Harry Campbell

Farhat Din

Malcolm Dunlop

Cite this