title: Genetic predictors of circulating 25-hydroxyvitamin d and risk of colorectal cancer.
abstract: BACKGROUND
  Experimental evidence has demonstrated an antineoplastic role for vitamin D in 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
  We investigated whether five polymorphisms in GC, CYP2R1, CYP24A1, and DHCR7/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
  We did 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.
  
  
  CONCLUSIONS
  There was no association observed between genetic markers of circulating 25(OH)D and colorectal cancer. These genetic markers account for a small proportion of the variance in 25(OH)D.
authors: Authors' Affiliations: Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Departments of Nutrition, and Biostatistics, Harvard School of Public Health; Department of Medicine, and Channing Division of Network Medicine, Brigham and Women's Hospital; Division of Gastroenterology, Massachusetts General Hospital; Department of Medicine, Harvard Medical School; Gastrointestinal Malignancy Program, and Medical-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Public Health Sciences Division, Fred Hutchinson Cancer Research Center; Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington; Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Divisions of Cancer Epidemiology and Genetics, and Cancer Control and Population Sciences, National Cancer Institute, NIH, Bethesda; University of Maryland, School of Medicine, Baltimore, Maryland; Service de Génétique Médicale, CHU Nantes, Nantes, France; Divisions of Clinical Epidemiology and Aging Research and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; Division of Research, Kaiser Permanente Medical Care Program, Oakland; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Translational Genomics Research Institute, Phoenix, Arizona; Department of Surgery, Toronto General Hospital; Ontario Institute for Cancer Research; Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto; Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada; Department of Environmental Medicine, Division of Epidemiology, New York University School of Medicine, New York; Department of Social and Preventive Medicine, University of Buffalo, Buffalo, New York; Melborne School of Population Health, The University of Melbourne, Melbourne, Victoria, Australia; Epidemiology Pro
authors: Linda T
authors: LT
authors: Hiraki
authors: Conghui
authors: C
authors: Qu
authors: Carolyn M
authors: CM
authors: Hutter
authors: John A
authors: JA
authors: Baron
authors: Sonja I
authors: SI
authors: Berndt
authors: Stéphane
authors: S
authors: Bézieau
authors: Hermann
authors: H
authors: Brenner
authors: Bette J
authors: BJ
authors: Caan
authors: Graham
authors: G
authors: Casey
authors: Jenny
authors: J
authors: Chang-Claude
authors: Stephen J
authors: SJ
authors: Chanock
authors: David V
authors: DV
authors: Conti
authors: David
authors: D
authors: Duggan
authors: Charles S
authors: CS
authors: Fuchs
authors: Steven
authors: S
authors: Gallinger
authors: Edward L
authors: EL
authors: Giovannucci
authors: Tabitha A
authors: TA
authors: Harrison
authors: Richard B
authors: RB
authors: Hayes
authors: Aditi
authors: A
authors: Hazra
authors: Brian
authors: B
authors: Henderson
authors: Michael
authors: M
authors: Hoffmeister
authors: John L
authors: JL
authors: Hopper
authors: Thomas J
authors: TJ
authors: Hudson
authors: Mark A
authors: MA
authors: Jenkins
authors: Sébastien
authors: S
authors: Küry
authors: Loic
authors: L
authors: Le Marchand
authors: Mathieu
authors: M
authors: Lemire
authors: Jing
authors: J
authors: Ma
authors: Joann E
authors: JE
authors: Manson
authors: Hongmei
authors: H
authors: Nan
authors: Polly A
authors: PA
authors: Newcomb
authors: Kimmie
authors: K
authors: Ng
authors: John D
authors: JD
authors: Potter
authors: Robert E
authors: RE
authors: Schoen
authors: Fredrick R
authors: FR
authors: Schumacher
authors: Daniela
authors: D
authors: Seminara
authors: Martha L
authors: ML
authors: Slattery
authors: Jean
authors: J
authors: Wactawski-Wende
authors: Emily
authors: E
authors: White
authors: Kana
authors: K
authors: Wu
authors: Brent W
authors: BW
authors: Zanke
authors: Peter
authors: P
authors: Kraft
authors: Ulrike
authors: U
authors: Peters
authors: Andrew T
authors: AT
authors: Chan
mesh_terms: D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics*; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
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