Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study.
OBJECTIVE
To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations.


METHODS
Nested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries.


METHODS
1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls


METHODS
Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders.


RESULTS
25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); >or=100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation.


CONCLUSIONS
The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.
Jenab
Mazda
M
International Agency for Research on Cancer (IARC-WHO), Lyon, France. Jenab@iarc.fr
Bueno-de-Mesquita
H Bas
HB
Ferrari
Pietro
P
van Duijnhoven
Franzel J B
FJ
Norat
Teresa
T
Pischon
Tobias
T
Jansen
Eugène H J M
EH
Slimani
Nadia
N
Byrnes
Graham
G
Rinaldi
Sabina
S
Tjønneland
Anne
A
Olsen
Anja
A
Overvad
Kim
K
Boutron-Ruault
Marie-Christine
MC
Clavel-Chapelon
Françoise
F
Morois
Sophie
S
Kaaks
Rudolf
R
Linseisen
Jakob
J
Boeing
Heiner
H
Bergmann
Manuela M
MM
Trichopoulou
Antonia
A
Misirli
Gesthimani
G
Trichopoulos
Dimitrios
D
Berrino
Franco
F
Vineis
Paolo
P
Panico
Salvatore
S
Palli
Domenico
D
Tumino
Rosario
R
Ros
Martine M
MM
van Gils
Carla H
CH
Peeters
Petra H
PH
Brustad
Magritt
M
Lund
Eiliv
E
Tormo
María-José
MJ
Ardanaz
Eva
E
Rodríguez
Laudina
L
Sánchez
Maria-José
MJ
Dorronsoro
Miren
M
Gonzalez
Carlos A
CA
Hallmans
Göran
G
Palmqvist
Richard
R
Roddam
Andrew
A
Key
Timothy J
TJ
Khaw
Kay-Tee
KT
Autier
Philippe
P
Hainaut
Pierre
P
Riboli
Elio
E
D002118:Calcium / Q000008:administration & dosage; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000453:epidemiology*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014807:Vitamin D / Q000008:administration & dosage / Q000097:blood*
D014807:Vitamin D; D002118:Calcium