Vitamin D receptor and calcium sensing receptor polymorphisms and the risk of colorectal cancer in European populations.
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.
Jenab
Mazda
M
Lifestyle and Cancer Group, IARC, 150 Cours Albert Thomas, 69008, Lyon, France. jenab@iarc.fr
McKay
James
J
Bueno-de-Mesquita
Hendrik B
HB
van Duijnhoven
Franzel J B
FJ
Ferrari
Pietro
P
Slimani
Nadia
N
Jansen
Eugène H J M
EH
Pischon
Tobias
T
Rinaldi
Sabina
S
Tjønneland
Anne
A
Olsen
Anja
A
Overvad
Kim
K
Boutron-Ruault
Marie-Christine
MC
Clavel-Chapelon
Françoise
F
Engel
Pierre
P
Kaaks
Rudolf
R
Linseisen
Jakob
J
Boeing
Heiner
H
Fisher
Eva
E
Trichopoulou
Antonia
A
Dilis
Vardis
V
Oustoglou
Erifili
E
Berrino
Franco
F
Vineis
Paolo
P
Mattiello
Amalia
A
Masala
Giovanna
G
Tumino
Rosario
R
Vrieling
Alina
A
van Gils
Carla H
CH
Peeters
Petra H
PH
Brustad
Magritt
M
Lund
Eiliv
E
Chirlaque
María-Dolores
MD
Barricarte
Aurelio
A
Suárez
Laudina Rodríguez
LR
Molina
Esther
E
Dorronsoro
Miren
M
Sala
Núria
N
Hallmans
Göran
G
Palmqvist
Richard
R
Roddam
Andrew
A
Key
Timothy J
TJ
Khaw
Kay-Tee
KT
Bingham
Sheila
S
Boffetta
Paolo
P
Autier
Philippe
P
Byrnes
Graham
G
Norat
Teresa
T
Riboli
Elio
E
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
D002136:Calcium, Dietary; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D014807:Vitamin D