Genetic predictors of circulating 25-hydroxyvitamin D and risk of colorectal cancer

Linda T. Hiraki, Conghui Qu, Carolyn M. Hutter, John A. Baron, Sonja I. Berndt, Stéphane Bézieau, Hermann Brenner, Bette J. Caan, Graham Casey, Jenny Chang-Claude, Stephen J. Chanock, David V. Conti, David Duggan, Charles S. Fuchs, Steven Gallinger, Edward L. Giovannucci, Tabitha A. Harrison, Richard B. Hayes, Aditi Hazra, Brian HendersonMichael Hoffmeister, John L. Hopper, Thomas J. Hudson, Mark A. Jenkins, Sebastien Küry, Loic Le Marchand, Mathieu Lemire, Jing Ma, Jo Ann E. Manson, Hongmei Nan, Polly A. Newcomb, Kimmie Ng, John D. Potter, Robert E. Schoen, Fredrick R. Schumacher, Daniela Seminara, Martha L. Slattery, Jean Wactawski-Wende, Emily White, Kana Wu, Brent W. Zanke, Peter Kraft, Ulrike Peters, Andrew T. Chan

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Experimental evidence has demonstrated an antineoplastic role for vitaminDin the colon, and higher circulating 25-hydroxyvitamin D [25(OH)D] levels are consistently associated with a lower risk of colorectal cancer. Genome-wide association studies have identified loci associated with levels of circulating 25(OH)D. The identified single-nucleotide polymorphisms (SNPs) from four gene regions collectively explain approximately 5% of the variance in circulating 25(OH)D. Methods:Weinvestigated whether five polymorphisms inGC, CYP2R1, CYP24A1, andDHCR7/NADSYN1, genes previously shown to be associated with circulating 25(OH)D levels, were associated with colorectal cancer risk in 10,061 cases and 12,768 controls drawn from 13 studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR). We conducted a meta-analysis of crude and multivariate- adjusted logistic regression models to calculate odds ratios and associated confidence intervals for SNPs individually, SNPs simultaneously, and for a vitamin D additive genetic risk score (GRS). Results:Wedid not observe a statistically significant association between the 25(OH)D-associated SNPs and colorectal cancer marginally, conditionally, or as a GRS, or for colon or rectal cancer separately. Conclusions: Our findings do not support an association between SNPs associated with circulating 25(OH)D and risk of colorectal cancer. Additional work is warranted to investigate the complex relationship between 25 (OH)D and colorectal cancer risk.

Original languageEnglish (US)
Pages (from-to)2037-2046
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number11
DOIs
StatePublished - Nov 1 2013
Externally publishedYes

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Colorectal Neoplasms
Single Nucleotide Polymorphism
Colonic Neoplasms
Logistic Models
Molecular Epidemiology
Genome-Wide Association Study
Rectal Neoplasms
Vitamin D
Antineoplastic Agents
Genes
Registries
Meta-Analysis
25-hydroxyvitamin D
Colon
Odds Ratio
Confidence Intervals

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Hiraki, L. T., Qu, C., Hutter, C. M., Baron, J. A., Berndt, S. I., Bézieau, S., ... Chan, A. T. (2013). Genetic predictors of circulating 25-hydroxyvitamin D and risk of colorectal cancer. Cancer Epidemiology Biomarkers and Prevention, 22(11), 2037-2046. https://doi.org/10.1158/1055-9965.EPI-13-0209

Genetic predictors of circulating 25-hydroxyvitamin D and risk of colorectal cancer. / Hiraki, Linda T.; Qu, Conghui; Hutter, Carolyn M.; Baron, John A.; Berndt, Sonja I.; Bézieau, Stéphane; Brenner, Hermann; Caan, Bette J.; Casey, Graham; Chang-Claude, Jenny; Chanock, Stephen J.; Conti, David V.; Duggan, David; Fuchs, Charles S.; Gallinger, Steven; Giovannucci, Edward L.; Harrison, Tabitha A.; Hayes, Richard B.; Hazra, Aditi; Henderson, Brian; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jenkins, Mark A.; Küry, Sebastien; Marchand, Loic Le; Lemire, Mathieu; Ma, Jing; Manson, Jo Ann E.; Nan, Hongmei; Newcomb, Polly A.; Ng, Kimmie; Potter, John D.; Schoen, Robert E.; Schumacher, Fredrick R.; Seminara, Daniela; Slattery, Martha L.; Wactawski-Wende, Jean; White, Emily; Wu, Kana; Zanke, Brent W.; Kraft, Peter; Peters, Ulrike; Chan, Andrew T.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 22, No. 11, 01.11.2013, p. 2037-2046.

Research output: Contribution to journalArticle

Hiraki, LT, Qu, C, Hutter, CM, Baron, JA, Berndt, SI, Bézieau, S, Brenner, H, Caan, BJ, Casey, G, Chang-Claude, J, Chanock, SJ, Conti, DV, Duggan, D, Fuchs, CS, Gallinger, S, Giovannucci, EL, Harrison, TA, Hayes, RB, Hazra, A, Henderson, B, Hoffmeister, M, Hopper, JL, Hudson, TJ, Jenkins, MA, Küry, S, Marchand, LL, Lemire, M, Ma, J, Manson, JAE, Nan, H, Newcomb, PA, Ng, K, Potter, JD, Schoen, RE, Schumacher, FR, Seminara, D, Slattery, ML, Wactawski-Wende, J, White, E, Wu, K, Zanke, BW, Kraft, P, Peters, U & Chan, AT 2013, 'Genetic predictors of circulating 25-hydroxyvitamin D and risk of colorectal cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 22, no. 11, pp. 2037-2046. https://doi.org/10.1158/1055-9965.EPI-13-0209
Hiraki, Linda T. ; Qu, Conghui ; Hutter, Carolyn M. ; Baron, John A. ; Berndt, Sonja I. ; Bézieau, Stéphane ; Brenner, Hermann ; Caan, Bette J. ; Casey, Graham ; Chang-Claude, Jenny ; Chanock, Stephen J. ; Conti, David V. ; Duggan, David ; Fuchs, Charles S. ; Gallinger, Steven ; Giovannucci, Edward L. ; Harrison, Tabitha A. ; Hayes, Richard B. ; Hazra, Aditi ; Henderson, Brian ; Hoffmeister, Michael ; Hopper, John L. ; Hudson, Thomas J. ; Jenkins, Mark A. ; Küry, Sebastien ; Marchand, Loic Le ; Lemire, Mathieu ; Ma, Jing ; Manson, Jo Ann E. ; Nan, Hongmei ; Newcomb, Polly A. ; Ng, Kimmie ; Potter, John D. ; Schoen, Robert E. ; Schumacher, Fredrick R. ; Seminara, Daniela ; Slattery, Martha L. ; Wactawski-Wende, Jean ; White, Emily ; Wu, Kana ; Zanke, Brent W. ; Kraft, Peter ; Peters, Ulrike ; Chan, Andrew T. / Genetic predictors of circulating 25-hydroxyvitamin D and risk of colorectal cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2013 ; Vol. 22, No. 11. pp. 2037-2046.
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title = "Genetic predictors of circulating 25-hydroxyvitamin D and risk of colorectal cancer",
abstract = "Background: Experimental evidence has demonstrated an antineoplastic role for vitaminDin the colon, and higher circulating 25-hydroxyvitamin D [25(OH)D] levels are consistently associated with a lower risk of colorectal cancer. Genome-wide association studies have identified loci associated with levels of circulating 25(OH)D. The identified single-nucleotide polymorphisms (SNPs) from four gene regions collectively explain approximately 5{\%} of the variance in circulating 25(OH)D. Methods:Weinvestigated whether five polymorphisms inGC, CYP2R1, CYP24A1, andDHCR7/NADSYN1, genes previously shown to be associated with circulating 25(OH)D levels, were associated with colorectal cancer risk in 10,061 cases and 12,768 controls drawn from 13 studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR). We conducted a meta-analysis of crude and multivariate- adjusted logistic regression models to calculate odds ratios and associated confidence intervals for SNPs individually, SNPs simultaneously, and for a vitamin D additive genetic risk score (GRS). Results:Wedid not observe a statistically significant association between the 25(OH)D-associated SNPs and colorectal cancer marginally, conditionally, or as a GRS, or for colon or rectal cancer separately. Conclusions: Our findings do not support an association between SNPs associated with circulating 25(OH)D and risk of colorectal cancer. Additional work is warranted to investigate the complex relationship between 25 (OH)D and colorectal cancer risk.",
author = "Hiraki, {Linda T.} and Conghui Qu and Hutter, {Carolyn M.} and Baron, {John A.} and Berndt, {Sonja I.} and St{\'e}phane B{\'e}zieau and Hermann Brenner and Caan, {Bette J.} and Graham Casey and Jenny Chang-Claude and Chanock, {Stephen J.} and Conti, {David V.} and David Duggan and Fuchs, {Charles S.} and Steven Gallinger and Giovannucci, {Edward L.} and Harrison, {Tabitha A.} and Hayes, {Richard B.} and Aditi Hazra and Brian Henderson and Michael Hoffmeister and Hopper, {John L.} and Hudson, {Thomas J.} and Jenkins, {Mark A.} and Sebastien K{\"u}ry and Marchand, {Loic Le} and Mathieu Lemire and Jing Ma and Manson, {Jo Ann E.} and Hongmei Nan and Newcomb, {Polly A.} and Kimmie Ng and Potter, {John D.} and Schoen, {Robert E.} and Schumacher, {Fredrick R.} and Daniela Seminara and Slattery, {Martha L.} and Jean Wactawski-Wende and Emily White and Kana Wu and Zanke, {Brent W.} and Peter Kraft and Ulrike Peters and Chan, {Andrew T.}",
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T1 - Genetic predictors of circulating 25-hydroxyvitamin D and risk of colorectal cancer

AU - Hiraki, Linda T.

AU - Qu, Conghui

AU - Hutter, Carolyn M.

AU - Baron, John A.

AU - Berndt, Sonja I.

AU - Bézieau, Stéphane

AU - Brenner, Hermann

AU - Caan, Bette J.

AU - Casey, Graham

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J.

AU - Conti, David V.

AU - Duggan, David

AU - Fuchs, Charles S.

AU - Gallinger, Steven

AU - Giovannucci, Edward L.

AU - Harrison, Tabitha A.

AU - Hayes, Richard B.

AU - Hazra, Aditi

AU - Henderson, Brian

AU - Hoffmeister, Michael

AU - Hopper, John L.

AU - Hudson, Thomas J.

AU - Jenkins, Mark A.

AU - Küry, Sebastien

AU - Marchand, Loic Le

AU - Lemire, Mathieu

AU - Ma, Jing

AU - Manson, Jo Ann E.

AU - Nan, Hongmei

AU - Newcomb, Polly A.

AU - Ng, Kimmie

AU - Potter, John D.

AU - Schoen, Robert E.

AU - Schumacher, Fredrick R.

AU - Seminara, Daniela

AU - Slattery, Martha L.

AU - Wactawski-Wende, Jean

AU - White, Emily

AU - Wu, Kana

AU - Zanke, Brent W.

AU - Kraft, Peter

AU - Peters, Ulrike

AU - Chan, Andrew T.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Background: Experimental evidence has demonstrated an antineoplastic role for vitaminDin the colon, and higher circulating 25-hydroxyvitamin D [25(OH)D] levels are consistently associated with a lower risk of colorectal cancer. Genome-wide association studies have identified loci associated with levels of circulating 25(OH)D. The identified single-nucleotide polymorphisms (SNPs) from four gene regions collectively explain approximately 5% of the variance in circulating 25(OH)D. Methods:Weinvestigated whether five polymorphisms inGC, CYP2R1, CYP24A1, andDHCR7/NADSYN1, genes previously shown to be associated with circulating 25(OH)D levels, were associated with colorectal cancer risk in 10,061 cases and 12,768 controls drawn from 13 studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR). We conducted a meta-analysis of crude and multivariate- adjusted logistic regression models to calculate odds ratios and associated confidence intervals for SNPs individually, SNPs simultaneously, and for a vitamin D additive genetic risk score (GRS). Results:Wedid not observe a statistically significant association between the 25(OH)D-associated SNPs and colorectal cancer marginally, conditionally, or as a GRS, or for colon or rectal cancer separately. Conclusions: Our findings do not support an association between SNPs associated with circulating 25(OH)D and risk of colorectal cancer. Additional work is warranted to investigate the complex relationship between 25 (OH)D and colorectal cancer risk.

AB - Background: Experimental evidence has demonstrated an antineoplastic role for vitaminDin the colon, and higher circulating 25-hydroxyvitamin D [25(OH)D] levels are consistently associated with a lower risk of colorectal cancer. Genome-wide association studies have identified loci associated with levels of circulating 25(OH)D. The identified single-nucleotide polymorphisms (SNPs) from four gene regions collectively explain approximately 5% of the variance in circulating 25(OH)D. Methods:Weinvestigated whether five polymorphisms inGC, CYP2R1, CYP24A1, andDHCR7/NADSYN1, genes previously shown to be associated with circulating 25(OH)D levels, were associated with colorectal cancer risk in 10,061 cases and 12,768 controls drawn from 13 studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR). We conducted a meta-analysis of crude and multivariate- adjusted logistic regression models to calculate odds ratios and associated confidence intervals for SNPs individually, SNPs simultaneously, and for a vitamin D additive genetic risk score (GRS). Results:Wedid not observe a statistically significant association between the 25(OH)D-associated SNPs and colorectal cancer marginally, conditionally, or as a GRS, or for colon or rectal cancer separately. Conclusions: Our findings do not support an association between SNPs associated with circulating 25(OH)D and risk of colorectal cancer. Additional work is warranted to investigate the complex relationship between 25 (OH)D and colorectal cancer risk.

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DO - 10.1158/1055-9965.EPI-13-0209

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