Vitamin D receptor gene polymorphisms and haplotypes and postmenopausal breast cancer risk.
BACKGROUND
Vitamin D receptor (VDR) genotypes may influence breast cancer risk by altering potential anticarcinogenic effects of vitamin D, but epidemiological studies have been inconsistent. Effect modification by serum 25-hydroxyvitamin D (25 [OH]D), the biomarker for vitamin D status in humans, has rarely been examined.


METHODS
We assessed the effects of two frequently analyzed polymorphisms (FokI and TaqI) and two potentially functional variants (VDR-5132 and Cdx2) in the VDR gene, which thus far have not been analyzed with respect to breast cancer risk, on postmenopausal breast cancer risk in a population-based, case-control study including 1,408 patients (cases) and 2,612 control individuals (controls) matched for year of birth. Odds ratios (ORs) for breast cancer adjusted for potential confounders were calculated for genotypes and estimated haplotypes.


RESULTS
No differences in serum 25(OD)D concentrations by VDR genotype were observed. None of the analyzed polymorphisms was associated with overall risk for postmenopausal breast cancer. However, the TaqI polymorphism was associated with a significantly increased risk for oestrogen receptor positive tumours (OR = 1.18, 95% confidence interval [CI] = 1.00 to 1.38, comparing t allele carriers with noncarriers) but not for oestrogen receptor negative tumours (OR = 0.88, 95% CI = 0.69 to 1.13; P for interaction = 0.04). Haplotype analysis revealed the haplotype FtCA (FokI F, TaqI t, VDR-5132 C, Cdx2 A), which contains the TaqI t allele, to be associated with a significantly greater breast cancer risk as compared with the most frequent haplotype FTCG (OR = 1.43, 95% CI = 1.00 to 2.05). No significant interaction between VDR genotypes or haplotypes and 25(OH)D was observed.


CONCLUSIONS
Our results support potential effects of VDR polymorphisms on postmenopausal breast cancer risk and possible differential effects of receptor status of the tumour. However, further studies focusing on the influence of polymorphisms and haplotypes on VDR functionality, activity and concentration are needed.
Abbas
Sascha
S
Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld, 69120 Heidelberg, Germany.
Nieters
Alexandra
A
Linseisen
Jakob
J
Slanger
Tracy
T
Kropp
Silke
S
Mutschelknauss
Elke Jonny
EJ
Flesch-Janys
Dieter
D
Chang-Claude
Jenny
J
D000368:Aged; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017698:Postmenopause; D018167:Receptors, Calcitriol / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D018167:Receptors, Calcitriol; D014807:Vitamin D; C104450:25-hydroxyvitamin D