Dairy products, polymorphisms in the vitamin D receptor gene and colorectal adenoma recurrence.
Vitamin D receptor (VDR) activation inhibits proliferation and angiogenesis in the colorectal epithelium, and inhibits metastasis of colorectal tumors. Polymorphisms in the VDR gene alter receptor cellular levels and functioning, and may confer altered susceptibility to colorectal neoplasia. We aimed to investigate the influence of VDR polymorphisms and dietary factors impacting on vitamin D metabolism on colorectal adenoma (CRA) recurrence. Data on dietary intakes of calcium, vitamin D and dairy products were collected from 853 participants in the United Kingdom Colorectal Adenoma Prevention trial, a randomized trial of aspirin and folate for CRA recurrence prevention. The VDR Cdx2, FokI, BsmI, ApaI and TaqI polymorphisms were genotyped in 546 participants with available DNA, and gene-diet interaction analyses performed in 480. Dairy product intake was inversely related to CRA recurrence risk independent of calcium and vitamin D [relative risk (RR) = 0.64; 95% confidence intervals (CIs): 0.47-0.88, for subjects in the highest compared to lowest intake tertile, p(trend) = 0.005]. Milk accounted for 60% of dairy product intake, and on analysis of milk and nonmilk dairy products separately recurrence risk in individuals in the highest tertile of milk intake was half that of lowest tertile individuals (RR = 0.52; 95% CI: 0.38-0.72, p(trend) = 3.2 x 10(-5)), whereas nonmilk dairy products did not influence recurrence. VDR polymorphism genotypes and haplotypes did not directly alter recurrence risk, but the reduction in risk associated with high dairy product intake was confined to individuals with ApaI aA/AA genotype (p(interaction) = 0.02). These findings indicate dairy products, and in particular milk, have chemopreventive activity against CRA recurrence.
Hubner
Richard A
RA
Institute of Cancer Research, Section of Cancer Genetics, Sutton SM2 5NG, United Kingdom. richard.hubner@icr.ac.uk
Muir
Kenneth R
KR
Liu
Jo-Fen
JF
Logan
Richard F A
RF
Grainge
Matthew J
MJ
Houlston
Richard S
RS
D000236:Adenoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D000328:Adult; D000368:Aged; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D017610:Calcium Compounds / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D003611:Dairy Products; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D008892:Milk; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D011110:Polymorphism, Genetic; D016032:Randomized Controlled Trials as Topic; D018167:Receptors, Calcitriol / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014157:Transcription Factors / Q000235:genetics*; D006113:United Kingdom; D014807:Vitamin D / Q000008:administration & dosage
D017610:Calcium Compounds; D018167:Receptors, Calcitriol; D014157:Transcription Factors; C467905:ZNF410 protein, human; D014807:Vitamin D; D005492:Folic Acid; D001241:Aspirin