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    Vitamin D receptor gene polymorphisms, insulin-like growth factors, and prostate cancer risk: A population-based case-control study in China

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    Author
    Chokkalingam, Anand P.
    Advisor
    Stolley, Paul D.
    Date
    2001
    Type
    dissertation
    
    Metadata
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    Abstract
    Background. Insulin-like growth factors (IGFs) have mitogenic and anti-apoptotic effects on prostate epithelial cells. Through modulation of IGF bioactivity, IGF binding proteins (IGFBPs) also have growth regulatory effects on prostate cells. Operating through the vitamin D receptor (VDR), vitamin D shows strong inhibitory effects on prostate cancer growth in both laboratory and human studies. Recent evidence indicates that vitamin D-induced prostate cancer inhibition is accompanied by increased IGFBP expression, suggesting that the vitamin D and IGF regulatory systems may operate together to affect prostate cancer. Methods. We sought to examine whether VDR gene polymorphisms affect prostate cancer risk -either independently or with plasma IGF or IGFBP levels - in a population-based case-control study in Shanghai, China. Histologically-confirmed cases of primary prostate cancer newly diagnosed between 1993 and 1995 (N = 191) and randomly selected age-matched population controls (N = 304) submitted to in-person interviews and blood draws. Genomic DNA was used to determine FokI and BsmI genotypes; IGF and IGFBP concentrations were determined from plasma. Results. No significant independent association of either the BsmI or the FokI VDR markers with prostate cancer was observed, though a small effect of BsmI cannot be ruled out owing to the low observed prevalence of its B allele. However, among men with the ff FokI genotype, those with the highest tertile of IGFBP-3 had a significantly decreased risk versus those with the lowest tertile (OR = 0.14; 95% CI = 0.04--0.56; ptrend < 0.01), while among men with the FF and Ff FokI genotypes IGFBP-3 was not associated with risk. Similarly, IGFBP-1 was significantly inversely associated with prostate cancer risk among men with the ff FokI genotype (OR = 0.25; 95% CI = 0.07--0.85; ptrend = 0.02), but not among men with the FF and Ff genotypes. No such FokI specific effects were noted for IGF-I or IGF-II. In addition, among population controls, IGF-II levels were significantly lower among those with the ff genotype versus the FF and Ff genotypes (p = 0.03), and IGFBP-1 levels appeared to increase with increasing copies of the f FokI allele. No associations between FokI genotype and levels of IGF-I of IGFBP-3 were observed. Conclusions. These findings in a low-risk population suggest that the IGF and vitamin D regulatory systems may interact to affect prostate cancer risk. Further studies are needed to confirm these findings and the clarify the underlying biological mechanisms.
    Description
    University of Maryland, Baltimore. Epidemiology and Preventive Medicine. Ph.D. 2001
    Keyword
    Health Sciences, Public Health
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/1219
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    Theses and Dissertations School of Medicine
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