title: Prospective associations between vitamin D status, vitamin D-related gene polymorphisms, and risk of tobacco-related cancers.
abstract: BACKGROUND
  Experimental evidence has suggested that vitamin D may be protective against tobacco-related cancers through the inhibition of the formation of tumors induced by tobacco carcinogens. To our knowledge, only one previous epidemiologic study investigated the association between vitamin D status and tobacco-related cancer risk, and no study has focused on vitamin D-related gene polymorphisms.
  
  
  OBJECTIVE
  Our objective was to prospectively study the association between plasma 25-hydroxyvitamin D [25(OH)D] concentrations, vitamin D-related gene polymorphisms, and risk of tobacco-related cancers.
  
  
  METHODS
  A total of 209 tobacco-related cancers were diagnosed within the SU.VI.MAX (Supplémentation en vitamines et minéraux antioxydants) cohort (1994-2007) and were matched with 418 controls as part of a nested case-control study. Tobacco-related cancers (i.e., cancers for which tobacco is one of the risk factors) included several sites in the respiratory, digestive, reproductive, and urinary systems. Total plasma 25(OH)D was assessed with the use of an electrochemoluminescent assay. Polymorphisms were determined with the use of a TaqMan assay. Conditional logistic regression models were computed.
  
  
  RESULTS
  A 25(OH)D concentration ≥30 ng/mL was associated with reduced risk of tobacco-related cancers (OR for ≥30 compared with <30 ng/mL: 0.59; 95% CI 0.35, 0.99; P = 0.046). This association was observed in former and current smokers (OR for ≥30 compared with <30 ng/mL: 0.43; 95% CI: 0.23, 0.84; P = 0.01) but not in never smokers (P = 0.8). The vitamin D receptor (VDR) FokI AA genotype and retinoid X receptor (RXR) rs7861779 TT genotype were associated with increased risk of tobacco-related cancers [OR for homozygous mutant type (MT) compared with wild type (WT): 1.87; 95% CI: 1.08, 3.23; P-trend = 0.02; OR for heterozygous type (HT) plus MT compared with WT: 1.60; 95% CI: 1.07, 2.38; P = 0.02].
  
  
  CONCLUSIONS
  In this prospective study, high vitamin D status [25(OH)D concentration ≥30 ng/mL] was associated with decreased risk of tobacco-related cancers, especially in smokers. These results, which are supported by mechanistic plausibility, suggest that vitamin D may contribute to the prevention of tobacco-induced cancers in smokers and deserve additional investigation. The SU.VI.MAX trial was registered at clinicaltrials.gov as NCT00272428.
authors.affiliation: Paris 13 University, Nutritional Epidemiology Research Team, French National Institute of Health and Medical Research (Inserm) U1153, French National Institute for Agricultural Research (Inra) U1125, French National Conservatory of Arts and Crafts (CNAM), Sorbonne Paris Cité University, Bobigny, France; m.deschasaux@eren.smbh.univ-paris13.fr.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Deschasaux
authors.affiliation: Physiology Department, Necker Hospital, Inserm U845, Paris, France;
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Souberbielle
authors.affiliation: Paris 13 University, Nutritional Epidemiology Research Team, French National Institute of Health and Medical Research (Inserm) U1153, French National Institute for Agricultural Research (Inra) U1125, French National Conservatory of Arts and Crafts (CNAM), Sorbonne Paris Cité University, Bobigny, France;
authors.forename: Paule
authors.initials: P
authors.lastname: Latino-Martel
authors.affiliation: Biochemistry Department, Jean Verdier Hospital, Inserm U698, Paris 13 University, Bondy, France;
authors.forename: Angela
authors.initials: A
authors.lastname: Sutton
authors.affiliation: Biochemistry Department, Jean Verdier Hospital, Inserm U698, Paris 13 University, Bondy, France;
authors.forename: Nathalie
authors.initials: N
authors.lastname: Charnaux
authors.affiliation: Paris 13 University, Nutritional Epidemiology Research Team, French National Institute of Health and Medical Research (Inserm) U1153, French National Institute for Agricultural Research (Inra) U1125, French National Conservatory of Arts and Crafts (CNAM), Sorbonne Paris Cité University, Bobigny, France;
authors.forename: Nathalie
authors.initials: N
authors.lastname: Druesne-Pecollo
authors.affiliation: Paris 13 University, Nutritional Epidemiology Research Team, French National Institute of Health and Medical Research (Inserm) U1153, French National Institute for Agricultural Research (Inra) U1125, French National Conservatory of Arts and Crafts (CNAM), Sorbonne Paris Cité University, Bobigny, France;
authors.forename: Pilar
authors.initials: P
authors.lastname: Galan
authors.affiliation: Paris 13 University, Nutritional Epidemiology Research Team, French National Institute of Health and Medical Research (Inserm) U1153, French National Institute for Agricultural Research (Inra) U1125, French National Conservatory of Arts and Crafts (CNAM), Sorbonne Paris Cité University, Bobigny, France; Public Health Department, Avicenne Hospital, Bobigny, France;
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.affiliation: CNAM, Genomics, Bioinformatics and Applications Team (EA4627), Paris, France; and.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Le Clerc
authors.affiliation: Paris 13 University, Nutritional Epidemiology Research Team, French National Institute of Health and Medical Research (Inserm) U1153, French National Institute for Agricultural Research (Inra) U1125, French National Conservatory of Arts and Crafts (CNAM), Sorbonne Paris Cité University, Bobigny, France;
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Kesse-Guyot
authors.affiliation: Paris 13 University, Nutritional Epidemiology Research Team, French National Institute of Health and Medical Research (Inserm) U1153, French National Institute for Agricultural Research (Inra) U1125, French National Conservatory of Arts and Crafts (CNAM), Sorbonne Paris Cité University, Bobigny, France; Dermatology Department, Saint André Hospital, Bordeaux, France.
authors.forename: Khaled
authors.initials: K
authors.lastname: Ezzedine
authors.affiliation: Paris 13 University, Nutritional Epidemiology Research Team, French National Institute of Health and Medical Research (Inserm) U1153, French National Institute for Agricultural Research (Inra) U1125, French National Conservatory of Arts and Crafts (CNAM), Sorbonne Paris Cité University, Bobigny, France;
authors.forename: Mathilde
authors.initials: M
authors.lastname: Touvier
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D000328:Adult; D000368:Aged; D002112:Calcifediol / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D009752:Nutritional Status; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D064424:Tobacco Use / Q000009:adverse effects*; D014808:Vitamin D Deficiency / Q000503:physiopathology*
chemical_list: D018167:Receptors, Calcitriol; D047490:Retinoid X Receptor alpha; C579457:VDR protein, human; D015652:25-Hydroxyvitamin D 2; D002112:Calcifediol
keywords: 25-hydroxyvitamin D; nested case-control study; single nucleotide polymorphisms; smoking status; tobacco-related cancers