Dairy products, polymorphisms in the vitamin D receptor gene and colorectal adenoma recurrence

Authors

  • Richard A. Hubner,

    Corresponding author
    1. Institute of Cancer Research, Section of Cancer Genetics, Sutton SM2 5NG, United Kingdom
    • Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
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  • Kenneth R. Muir,

    1. Division of Epidemiology and Public Health, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom
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  • Jo-Fen Liu,

    1. Division of Epidemiology and Public Health, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom
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  • Richard F.A. Logan,

    1. Division of Epidemiology and Public Health, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom
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  • Matthew J. Grainge,

    1. Division of Epidemiology and Public Health, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom
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  • Richard S. Houlston,

    1. Institute of Cancer Research, Section of Cancer Genetics, Sutton SM2 5NG, United Kingdom
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  • and Members of the UKCAP Consortium

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    • United Kingdom Colorectal Adenoma Prevention Trial Consortium members: N. Armitage, V. Shepherd, C. Elliott, P. Watmough, S. Barratt, N. Birch, A. Gibbons, G. Campion, University of Nottingham Medical School, Nottingham, UK; R. Logan, N. Wright, J. Patterson, Kings Mill Hospital, Sutton-In-Ashfield, UK; A. Scott, Glenfield Hospital, Leicester, UK; J. Reynolds, Derby City General Hospital and Derby Royal Infirmary, Derby, UK; R. Walt, H. Martin, B. Bisseker, Birmingham Heartlands Hospital, Birmingham, UK; N. Hudson, Birmingham City Hospital, Birmingham, UK; A. Hamlyn, Wordsley Hospital, Stourbridge, UK; M. Thomas, P. Durdey, K. Green, Bristol Royal Infirmary, Bristol, UK; A. Roe, Southmead Hospital, Bristol, UK; A. Watson, K. Johnston, Royal Liverpool University Hospital, Liverpool, UK; C. Babbs, Hope Hospital, Salford, UK; D. Shreeve, North Manchester General Hospital, Manchester, UK; J. Crampton, Wythenshawe Hospital, Manchester, UK; C. Summerton, Trafford General Hospital, Manchester, UK; T. Warnes, Manchester Royal Infirmary, Manchester, UK; P. Isaacs, M. Rolland, Blackpool Victoria Hospital, Blackpool, UK; A. Shorthouse, E. Heatherington, Royal Hallamshire Hospital, South Yorkshire, UK; K. Hosie, Northern General Hospital, South Yorkshire, UK; K. Bardhan, Rotherham District General Hospital, South Yorkshire, UK; K. Vellacott, D. Knight-Davis, Royal Gwent Hospital, Newport, UK; A. Hawthorne, H. Thompson-Jones, R. Stenson, University Hospital of Wales, Cardiff, UK; P. Watson, H. Lawther, Royal Victoria Hospital, Belfast, UK; O. Kronborg, Odense University Hospital, Odense, Denmark.


Abstract

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, ptrend = 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, ptrend = 3.2 × 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 (pinteraction = 0.02). These findings indicate dairy products, and in particular milk, have chemopreventive activity against CRA recurrence. © 2008 Wiley-Liss, Inc.

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