title: Vitamin D receptor and calcium sensing receptor polymorphisms and the risk of colorectal cancer in European populations.
abstract: Increased levels of vitamin D and calcium may play a protective role in colorectal cancer (CRC) risk. It has been suggested that these effects may be mediated by genetic variants of the vitamin D receptor (VDR) and the calcium sensing receptor (CASR). However, current epidemiologic evidence from European populations for a role of these genes in CRC risk is scarce. In addition, it is not clear whether these genes may modulate CRC risk independently or by interaction with blood vitamin D concentration and level of dietary calcium intake. A case-control study was conducted nested within the European Prospective Investigation into Cancer and Nutrition. CRC cases (1,248) were identified and matched to 1,248 control subjects. Genotyping for the VDR (BsmI: rs1544410; Fok1: rs2228570) and CASR (rs1801725) genes was done by Taqman, and serum vitamin D (25OHD) concentrations were measured. Conditional logistic regression was used to estimate the incidence rate ratio (RR). Compared with the wild-type bb, the BB genotype of the VDR BsmI polymorphism was associated with a reduced risk of CRC [RR, 0.76; 95% confidence interval (CI), 0.59-0.98). The association was observed for colon cancer (RR, 0.69; 95% CI, 0.45-0.95) but not rectal cancer (RR, 0.97; 95% CI, 0.62-1.49). The Fok1 and CASR genotypes were not associated with CRC risk in this study. No interactions were noted for any of the polymorphisms with serum 25OHD concentration or level of dietary calcium. These results confirm a role for the BsmI polymorphism of the VDR gene in CRC risk, independent of serum 25OHD concentration and dietary calcium intake.
authors.affiliation: Lifestyle and Cancer Group, IARC, 150 Cours Albert Thomas, 69008, Lyon, France. jenab@iarc.fr
authors.forename: Mazda
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authors.lastname: Jenab
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authors.lastname: Mattiello
authors.forename: Giovanna
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authors.forename: Rosario
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authors.forename: Alina
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authors.lastname: Vrieling
authors.forename: Carla H
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authors.lastname: van Gils
authors.forename: Petra H
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authors.lastname: Peeters
authors.forename: Magritt
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authors.lastname: Brustad
authors.forename: Eiliv
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authors.lastname: Lund
authors.forename: María-Dolores
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authors.lastname: Chirlaque
authors.forename: Aurelio
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authors.lastname: Barricarte
authors.forename: Laudina Rodríguez
authors.initials: LR
authors.lastname: Suárez
authors.forename: Esther
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authors.lastname: Molina
authors.forename: Miren
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authors.lastname: Dorronsoro
authors.forename: Núria
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authors.lastname: Sala
authors.forename: Göran
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authors.lastname: Hallmans
authors.forename: Richard
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authors.lastname: Palmqvist
authors.forename: Andrew
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authors.lastname: Roddam
authors.forename: Timothy J
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authors.lastname: Key
authors.forename: Kay-Tee
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authors.lastname: Khaw
authors.forename: Sheila
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authors.lastname: Bingham
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Philippe
authors.initials: P
authors.lastname: Autier
authors.forename: Graham
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authors.lastname: Byrnes
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mesh_terms: D002136:Calcium, Dietary / Q000008:administration & dosage; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D014807:Vitamin D / Q000097:blood; D044465:White People
chemical_list: D002136:Calcium, Dietary; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D014807:Vitamin D