Circulating vitamin D metabolites, polymorphism in vitamin D receptor, and colorectal adenoma risk.
OBJECTIVE
Vitamin D is a potential agent for the prevention of colorectal cancer possibly through mechanisms mediated by the vitamin D receptor (VDR). We investigated the association of circulating vitamin D metabolites and a genetic variant of the VDR gene with advanced colorectal adenoma, a precursor lesion of colorectal cancer.


METHODS
Cases with advanced adenoma of the distal large bowel and gender- and ethnicity-matched controls with a negative sigmoidoscopy were randomly selected from participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. Genotype analysis of the VDR TaqI polymorphism was completed on 763 cases and 774 controls. Serum levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured in a subset of 394 cases and 397 controls.


RESULTS
Serum levels of 25(OH)D were inversely associated with advanced adenoma risk in women but not in men. Comparing those in the highest quintile with those in the lowest quintile, the risk for advanced adenoma decreased by 73% in women [odds ratio (OR) = 0.27, 95% confidence interval (95% CI) = 0.11-0.69; P for trend = 0.0002], while the risk did not decrease in men (OR = 1.10, 95% CI = 0.60-2.05; P for trend = 0.85). In women, 25(OH)D levels were significantly higher in current users of hormone replacement therapy (HRT) than in former or never HRT users. Neither serum 1,25(OH)(2)D nor VDR TaqI genotype was associated with advanced adenoma risk.


CONCLUSIONS
Higher serum 25(OH)D levels were associated with decreased adenoma risk. Serum 1,25(OH)(2)D and VDR TaqI genotype were not associated with adenoma risk.
Peters
Ulrike
U
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH/DHHS, 6120 Executive Boulevard, EPS 3024, Rockville, MD 20852, USA. petersu@mail.nih.gov
Hayes
Richard B
RB
Chatterjee
Nilanjan
N
Shao
Wen
W
Schoen
Robert E
RE
Pinsky
Paul
P
Hollis
Bruce W
BW
McGlynn
Katherine A
KA
D000236:Adenoma / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011897:Random Allocation; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology; D014807:Vitamin D / Q000097:blood*
D018167:Receptors, Calcitriol; D014807:Vitamin D