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: Mazda Jenab, James McKay, Hendrik B Bueno-de-Mesquita, Franzel J B van Duijnhoven, Pietro Ferrari, Nadia Slimani, Eugène H J M Jansen, Tobias Pischon, Sabina Rinaldi, Anne Tjønneland, Anja Olsen, Kim Overvad, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Pierre Engel, Rudolf Kaaks, Jakob Linseisen, Heiner Boeing, Eva Fisher, Antonia Trichopoulou, Vardis Dilis, Erifili Oustoglou, Franco Berrino, Paolo Vineis, Amalia Mattiello, Giovanna Masala, Rosario Tumino, Alina Vrieling, Carla H van Gils, Petra H Peeters, Magritt Brustad, Eiliv Lund, María-Dolores Chirlaque, Aurelio Barricarte, Laudina Rodríguez Suárez, Esther Molina, Miren Dorronsoro, Núria Sala, Göran Hallmans, Richard Palmqvist, Andrew Roddam, Timothy J Key, Kay-Tee Khaw, Sheila Bingham, Paolo Boffetta, Philippe Autier, Graham Byrnes, Teresa Norat, Elio Riboli
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 18 Issue 9 Pg. 2485-91 (Sep 2009) ISSN: 1538-7755 [Electronic] United States
• PMID: 19706842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium, Dietary
• Receptors, Calcitriol
• Receptors, Calcium-Sensing
• Vitamin D

Topics

• Calcium, Dietary (administration & dosage)
• Case-Control Studies
• Colorectal Neoplasms (blood, epidemiology, genetics)
• Europe (epidemiology)
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Life Style
• Male
• Middle Aged
• Polymorphism, Genetic
• Receptors, Calcitriol (genetics)
• Receptors, Calcium-Sensing (genetics)
• Vitamin D (blood)
• White People