Vitamin D receptor polymorphisms and breast cancer risk: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.
BACKGROUND
Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR, and reduced risk has been reported for the BsmI BB genotype, a SNP in strong linkage disequilibrium with a 3'-untranslated region, which may influence VDR mRNA stability.


METHODS
We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression.


RESULTS
The odds ratio (OR) for the rs2228570 (FokI) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 (BsmI) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92).


CONCLUSIONS
Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status.
McKay
James D
JD
IARC, Lyon, France.
McCullough
Marjorie L
ML
Ziegler
Regina G
RG
Kraft
Peter
P
Saltzman
Barbara S
BS
Riboli
Elio
E
Barricarte
Aurelio
A
Berg
Christine D
CD
Bergland
Goran
G
Bingham
Sheila
S
Brustad
Magritt
M
Bueno-de-Mesquita
H Bas
HB
Burdette
Laurie
L
Buring
Julie
J
Calle
Eugenia E
EE
Chanock
Stephen J
SJ
Clavel-Chapelon
Françoise
F
Cox
David G
DG
Dossus
Laure
L
Feigelson
Heather Spencer
HS
Haiman
Christopher A
CA
Hankinson
Susan E
SE
Hoover
Robert N
RN
Hunter
David J
DJ
Husing
Anika
A
Kaaks
Rudolph
R
Kolonel
Laurence N
LN
Le Marchand
Loic
L
Linseisen
Jakob
J
McCarty
Catherine A
CA
Overvad
Kim
K
Panico
Salvatore
S
Purdue
Mark P
MP
Stram
Daniel O
DO
Stevens
Victoria L
VL
Trichopoulos
Dimitrios
D
Willett
Walter C
WC
Yuenger
Jeffrey
J
Thun
Michael J
MJ
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000235:genetics*; D012306:Risk
D018167:Receptors, Calcitriol