Vitamin D receptor haplotypes protect against development of colorectal cancer.
OBJECTIVE
We investigated the association of vitamin D receptor polymorphisms and colorectal cancer incidence in a Caucasian population.


METHODS
Frequencies of the vitamin D receptor gene polymorphisms 23005G>A (CDX-2), 27823C>T (FokI), 60890G>A (BsmI), 61050G>A (Tru9I), 61888G>T (ApaI), and 61968T>C (TaqI) were determined in a series of 256 colorectal cancer patients and 256 patients without malignant disease (case-control study) using polymerase chain reaction and restriction fragment length polymorphism genotyping assays (PCR-RFLP). Haplotype analysis based on the six genetic loci was applied to the received genotypes.


RESULTS
Pairwise linkage disequilibrium between BsmI, ApaI, TaqI, and Tru9I was confirmed (P < 0.001). Allele frequencies did not differ between the groups. There was no association between any single variant and colorectal cancer. However, haplotypes BsmI(G)#TaqI(C) and BsmI(A)#TaqI(T) were inversely associated with colorectal cancer incidence (P < 0.001), the odds being 15.0 times smaller [odds ratio (OR) 0.067; 95% confidence interval (CI), 0.016-0.284] and 5.3 times smaller (OR 0.188; 95% CI 0.077-0.461), respectively, compared with noncarriers.


CONCLUSIONS
Our findings suggest that vitamin D receptor haplotypes BsmI(G)#TaqI(C) and BsmI(A)#TaqI(T) have a protective effect against colorectal cancer in Caucasians.
Flügge
Jana
J
Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Charité Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany.
Krusekopf
Solveigh
S
Goldammer
Mark
M
Osswald
Elena
E
Terhalle
Werner
W
Malzahn
Uwe
U
Roots
Ivar
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018167:Receptors, Calcitriol / Q000235:genetics*; D044465:White People / Q000235:genetics
D018167:Receptors, Calcitriol